A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.
A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.
A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)
Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.
Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)
Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
Inherited disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. The different clinical types based on symptoms correspond to the presence of a variety of mutations in several different proteins including transthyretin (PREALBUMIN); APOLIPOPROTEIN A-I; and GELSOLIN.
A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.
Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
Diseases in which there is a familial pattern of AMYLOIDOSIS.
Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
A spectroscopic technique in which a range of wavelengths is presented simultaneously with an interferometer and the spectrum is mathematically derived from the pattern thus obtained.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.
A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.
An autosomal dominant familial prion disease with a wide spectrum of clinical presentations including ATAXIA, spastic paraparesis, extrapyramidal signs, and DEMENTIA. Clinical onset is in the third to sixth decade of life and the mean duration of illness prior to death is five years. Several kindreds with variable clinical and pathologic features have been described. Pathologic features include cerebral prion protein amyloidosis, and spongiform or neurofibrillary degeneration. (From Brain Pathol 1998 Jul;8(3):499-513; Brain Pathol 1995 Jan;5(1):61-75)
Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.
A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.
The rate dynamics in chemical or physical systems.
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
G-protein coupled receptors that are formed through the dimerization of the CALCITONIN RECEPTOR with a RECEPTOR ACTIVITY-MODIFYING PROTEIN. Their affinity for ISLET AMYLOID POLYPEPTIDE is dependent upon which of several receptor activity-modifying protein subtypes they are bound to.
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
Proteins prepared by recombinant DNA technology.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.
An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.
An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.
Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Elements of limited time intervals, contributing to particular results or situations.
The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
A non-aqueous co-solvent that serves as tool to study protein folding. It is also used in various pharmaceutical, chemical and engineering applications.
A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
Chemicals and substances that impart color including soluble dyes and insoluble pigments. They are used in INKS; PAINTS; and as INDICATORS AND REAGENTS.
Compounds with a benzene ring fused to a thiazole ring.
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.
Established cell cultures that have the potential to propagate indefinitely.

Islet amyloid polypeptide/amylin messenger RNA and protein expression in human insulinomas in relation to amyloid formation. (1/3010)

OBJECTIVE: Islet amyloid polypeptide (IAPP), also named amylin, is the predominant protein component of amyloid deposits in human islet beta cell tumours of the pancreas (insulinomas). IAPP is co-produced with insulin by islet beta cells. We investigated IAPP expression in relation to insulin expression and to amyloid formation in eleven insulinomas. DESIGN AND METHODS: RNA and protein extracts were prepared from the same pieces of tumour tissue, and from specimens of two normal human pancreata. IAPP and insulin mRNA and peptide content were quantified using Northern blot analysis and radioimmunoassay (RIA) respectively. Molecular forms of IAPP immunoreactivity were analysed by reversed-phase high-performance liquid chromatography (HPLC). The presence of islet hormones and of amyloid was assessed by (immuno)histochemical staining of paraffin sections. Plasma levels of IAPP and insulin prior to tumour resection were determined by RIA. RESULTS: IAPP and insulin mRNA and peptide content varied widely between the tumour specimens, and there was considerable intratumour heterogeneity of peptide content. HPLC analysis indicated correct proteolytic processing of the IAPP precursor protein. Amyloid deposits were detected only in the three tumours with the highest IAPP content. In contrast to insulin, plasma levels of IAPP were not elevated in the insulinoma patients. CONCLUSIONS: The spectrum of hormone production by insulinomas cannot be inferred from only a few tissue sections due to intratumour heterogeneity. Expression of the IAPP and insulin genes is not coupled in insulinomas, which produce properly processed mature IAPP. In addition to IAPP overproduction, additional factors such as intracellular accumulation of IAPP are involved in amyloidogenesis in insulinomas.  (+info)

Prion domain initiation of amyloid formation in vitro from native Ure2p. (2/3010)

The [URE3] non-Mendelian genetic element of Saccharomyces cerevisiae is an infectious protein (prion) form of Ure2p, a regulator of nitrogen catabolism. Here, synthetic Ure2p1-65 were shown to polymerize to form filaments 40 to 45 angstroms in diameter with more than 60 percent beta sheet. Ure2p1-65 specifically induced full-length native Ure2p to copolymerize under conditions where native Ure2p alone did not polymerize. Like Ure2p in extracts of [URE3] strains, these 180- to 220-angstrom-diameter filaments were protease resistant. The Ure2p1-65-Ure2p cofilaments could seed polymerization of native Ure2p to form thicker, less regular filaments. All filaments stained with Congo Red to produce the green birefringence typical of amyloid. This self-propagating amyloid formation can explain the properties of [URE3].  (+info)

Interaction of amylin with calcitonin gene-related peptide receptors in the microvasculature of the hamster cheek pouch in vivo. (3/3010)

1. This study used intravital microscopy to investigate the receptors stimulated by amylin which shares around 50% sequence homology with the vasodilator calcitonin gene-related peptide (CGRP) in the hamster cheek pouch microvasculature in vivo. 2. Receptor agonists dilated arterioles (diameters 20-40 microm). The -log of the concentrations (+/- s.e.mean; n = 8) causing 50% increase in arteriole diameter were: human betaCGRP (10.8 +/- 0.3), human alphaCGRP (10.8 +/- 0.4), rat alphaCGRP (10.4 +/- 0.3). Rat amylin and the CGRP2 receptor selective agonist [Cys(ACM2,7]-human alphaCGRP were 100 fold less potent (estimates were 8.5 +/- 0.4 and 8.2 +/- 0.3 respectively). 3. The GCRP1 receptor antagonist, CGRP8-37 (300 nmol kg(-1); i.v.) reversibly inhibited the increase in diameter evoked by human alphaCGRP (0.3 nM) from 178 +/- 22% to 59 +/- 12% (n = 8; P < 0.05) and by rat amylin (100 nM) from 138 +/- 23% to 68 +/- 24% (n = 6; P < 0.05). CGRP8-37 did not inhibit vasodilation evoked by substance P (10 nM; n = 4: P > 0.05). 4. The amylin receptor antagonist, amylin8-37 (300 nmol kg(-1); i.v.) did not significantly inhibit the increase in diameter evoked by human alphaCGRP (0.3 nM) which was 112 +/- 26% in the absence, and 90 +/- 29% in the presence of antagonist (n = 4; P < 0.05); nor that evoked by rat amylin (100 nM) which was 146 +/- 23% in the absence and 144 +/- 32% in the presence of antagonist (n = 4; P > 0.05). 5. The agonist profile for vasodilatation and the inhibition of this dilatation by CGRP8-37, although not the amylin8-37 indicates that amylin causes vasodilatation through interaction with CGRP1 receptors in the hamster cheek pouch.  (+info)

The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. (4/3010)

NIDDM is characterized by islet amyloid deposits and decreased beta-cell mass. Islet amyloid is derived from the locally expressed protein islet amyloid polypeptide (IAPP). While it is now widely accepted that abnormal aggregation of IAPP has a role in beta-cell death in NIDDM, the mechanism remains unknown. We hypothesized that small IAPP aggregates, rather than mature large amyloid deposits, are cytotoxic. Consistent with this hypothesis, freshly dissolved human (h)-IAPP was cytotoxic when added to dispersed mouse and human islet cells, provoking the formation of abnormal vesicle-like membrane structures in association with vacuolization and cell death. Human islet cell death occurred by both apoptosis and necrosis, predominantly between 24 and 48 h after exposure to h-IAPP. In contrast, the addition to dispersed islet cells of matured h-IAPP containing large amyloid deposits of organized fibrils was seldom associated with vesicle-like structures or features of cell death, even though the cells were often encased in the larger amyloid deposits. Based on these observations, we hypothesized that h-IAPP cytotoxicity is mediated by membrane damage induced by early h-IAPP aggregates. Consistent with this hypothesis, application of freshly dissolved h-IAPP to voltage-clamped planar bilayer membranes (a cell-free in vitro system) also caused membrane instability manifested as a marked increase in conductance, increased membrane electrical noise, and accelerated membrane breakage, effects that were absent using matured h-IAPP or rat IAPP solutions. Light-scattering techniques showed that membrane toxicity corresponded to h-IAPP aggregates containing approximately 25-6,000 IAPP molecules, an intermediate-sized amyloid particle that we term intermediate-sized toxic amyloid particles (ISTAPs). We conclude that freshly dissolved h-IAPP is cytotoxic and that this cytotoxicity is mediated through an interaction of ISTAPs with cellular membranes. Once ISTAPs mature into amyloid deposits comprising >10(6) molecules, the capacity of h-IAPP to cause membrane instability and islet cell death is significantly reduced or abolished. These data may have implications for the mechanism of cell death in other diseases characterized by local amyloid formation (such as Alzheimer's disease).  (+info)

Specific gene expression in pancreatic beta-cells: cloning and characterization of differentially expressed genes. (5/3010)

Identification and characterization of genes expressed preferentially in pancreatic beta-cells will clarify the mechanisms involved in the specialized properties of these cells, as well as providing new markers of the development of type 1 diabetes. Despite major efforts, relatively few beta-cell-specific genes have been characterized. We applied representational difference analysis to identify genes expressed selectively in the pancreatic beta-cell line betaTC1 compared with the pancreatic alpha-cell line alphaTC1 and isolated 26 clones expressed at higher levels in the beta-cells than in the alpha-cells. DNA sequencing revealed that 14 corresponded to known genes (that is, present in GenBank). Only four of those genes had been shown previously to be expressed at higher levels in beta-cells (insulin, islet amyloid polypeptide, neuronatin, and protein kinase A regulatory subunit [RIalpha]). The known genes include transcription factors (STAT6) and mediators of signal transduction (guanylate cyclase). The remaining 12 genes are absent from the GenBank database or are present as expressed sequence tag (EST) sequences (4 clones). Some of the genes are expressed in a highly specific pattern-expression in betaTC1 and islet cells and in relatively few of the non-beta-cell types examined; others are expressed in most cell types tested. The identification of these differentially expressed genes may aid in attaining a clearer understanding of the mechanisms involved in beta-cell function and of the possible immunogens involved in development of type 1 diabetes.  (+info)

Colchicine inhibition of the first phase of amyloid synthesis in experimental animals. (6/3010)

Colchicine was found to inhibit the first phase of casein-induced synthesis of murine amyloid. When mice were treated with colchicine during the first 7 days of an amyloid induction regimen or when colchicine was given to the donor mice in a transfer model, the amyloidogenic stimulus of casein was blocked completely. Amyloid synthesis was however, not interrupted by the administration of colchicine during the last 7 days of the casein regimen nor by colchicine treatment of recipient mice in a transfer model.  (+info)

Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease. (7/3010)

Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the basis of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation.  (+info)

Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains. (8/3010)

The most common form of systemic amyloidosis originates from antibody light chains. The large number of amino acid variations that distinguish amyloidogenic from nonamyloidogenic light chain proteins has impeded our understanding of the structural basis of light-chain fibril formation. Moreover, even among the subset of human light chains that are amyloidogenic, many primary structure differences are found. We compared the thermodynamic stabilities of two recombinant kappa4 light-chain variable domains (V(L)s) derived from amyloidogenic light chains with a V(L) from a benign light chain. The amyloidogenic V(L)s were significantly less stable than the benign V(L). Furthermore, only the amyloidogenic V(L)s formed fibrils under native conditions in an in vitro fibril formation assay. We used site-directed mutagenesis to examine the consequences of individual amino acid substitutions found in the amyloidogenic V(L)s on stability and fibril formation capability. Both stabilizing and destabilizing mutations were found; however, only destabilizing mutations induced fibril formation in vitro. We found that fibril formation by the benign V(L) could be induced by low concentrations of a denaturant. This indicates that there are no structural or sequence-specific features of the benign V(L) that are incompatible with fibril formation, other than its greater stability. These studies demonstrate that the V(L) beta-domain structure is vulnerable to destabilizing mutations at a number of sites, including complementarity determining regions (CDRs), and that loss of variable domain stability is a major driving force in fibril formation.  (+info)

If you have a question about this talk, please contact Dr Georg Krainer.. Many bacteria produce functional amyloid, i.e. proteins which are secreted through dedicated export systems and self-assemble on the bacterial surface, often with the help of nucleator proteins. These amyloid proteins serve a diversity of purposes, but the most prominent one appears to be structural stability; for example, overexpression of the amyloid-forming protein FapC in Pseudomonas species strengthens bacterial biofilm against mechanical insults, increases hydrophobicity and protects against desiccation. Similar properties are ascribed to the curli-forming protein CsgA from E. coli. Unlike pathological amyloid, functional amyloid has been under evolutionary pressure to self-assemble efficiently (i.e. in a single fast track) to very stable higher-order structures. My lab is engaged in an effort to understand the molecular basis for these properties in more detail and I will present recent progress in this ...
We have revisited the well-studied heat and acidic amyloid fibril formation pathway (pH 1.6, 65 °C) of hen egg-white lysozyme (HEWL) to map the barriers of the misfolding and amyloidogenesis pathways. A comprehensive kinetic mechanism is presented where all steps involving protein hydrolysis, fragmentation, assembly and conversion into amyloid fibrils are accounted for. Amyloid fibril formation of lysozyme has multiple kinetic barriers. First, HEWL unfolds within minutes, followed by irreversible steps of partial acid hydrolysis affording a large amount of nicked HEWL, the 49-101 amyloidogenic fragment and a variety of other species over 5-40 h. Fragmentation forming the 49-101 fragment is a requirement for efficient amyloid fibril formation, indicating that it forms the rate-determining nucleus. Nicked full-length HEWL is recruited efficiently into amyloid fibrils in the fibril growth phase or using mature fibrils as seeds, which abolished the lag phase completely. Mature amyloid fibrils of ...
Gerstmann-Sträussler-Scheinker disease (GSS) is a prion-related encephalopathy pathologically characterized by massive deposition of prion protein (PrP) amyloid in the central nervous system. The major component of amyloid fibrils isolated from patients of the Indiana kindred of GSS (GSS-Ik) is an 11-kDa fragment of PrP spanning residues 58 to approximately 150. These patients carry a missense mutation of the PRNP gene, causing a Phe--,Ser substitution at codon 198. We investigated fibrillogenesis in vitro by using synthetic peptides homologous to consecutive segments of GSS-Ik amyloid protein (residues 57-64, 89-106, 106-126, and 127-147) as well as peptides from the PrP region with the GSS-Ik mutation (residues 191-205 and 181-205, both wild type and mutant). Peptide PrP-(106-126) formed straight fibrils similar to those extracted from GSS brains, whereas peptide PrP-(127-147) formed twisted fibrils resembling scrapie-associated fibrils isolated from subjects with transmissible spongiform ...
Amyloid formation is inherent property of proteins which under certain circumstances can become a pathologic feature of a group of diseases called amyloidosis. There are about 30 known human amyloidosis and more than 27 identified proteins involved in these pathologies. Besides these proteins, there are a growing number of proteins non-related to diseases shown to form amyloid-like structures in vitro, which make them excellent tools for studying amyloid formation mechanisms, physicochemical properties of different amyloid species and the nature of their influence on tissues and cells. It is important to understand the mechanisms by which amyloids interact with different types of cells, as the leading hypothesis in amyloid field suggests that amyloids and especially their intermediate states are the main harmful, toxic species causing tissue and cell degeneration.. Using de-novo synthesized protein albebetin as a model of amyloidogenic protein, we demonstrated that it forms amyloid-like ...
Author: Olzscha, H. et al.; Genre: Journal Article; Published in Print: 2011-01-07; Title: Amyloid-like Aggregates Sequester Numerous Metastable Proteins with Essential Cellular Functions
p,Protein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. β-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from Aβ and tau were incorporated into macrocycles, thereby restraining them to β-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which β-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a ...
The structures of amyloid fibrils and oligomers represent a vast frontier, of yet unknown scope. The fibrils and aggregates that amyloidogenic peptides and proteins form are rich in β-sheets, and their structures are tremendously important in amyloid diseases. Many structures of amyloid fibrils have been discovered by solid-state NMR spectroscopy of amyloidogenic peptides and proteins and by X-ray crystallography of smaller fragments.1-4 Studying amyloid oligomer structures at high resolution is challenging, because amyloid oligomers are heterogeneous and dynamic, forming various species of different sizes and morphologies. Although a few structures of amyloid oligomers have been discovered in the last decade, there are not enough to provide a full understanding of amyloid assemblies.5-7 Our laboratory has pioneered the use of macrocyclic β-sheets as a tool for exploring the structures of amyloid oligomers. In collaboration with the Eisenberg group, we began using X-ray crystallography to ...
The use of small carbohydrates that stabilize proteins from misfolding is important from pharmaceutical point of view. We have investigated the role of small isomeric amino sugars on the in vitro aggregation of insulin amyloid. Using mass spectrometry, we screened 6 isomeric aminosugars for their role on inhibition of insulin amyloid formation and the results were compared with transmission electron microscopy imaging. We found that three N-acetylamino sugars promote insulin fibril formation. Among three isomeric aminosugars studied, only galactosamine showed few fibrils whereas other two isomers showed enhanced fibrils. The results demonstrated here may contribute to future designing of small amine derivatised galactose sugars as amyloid inhibitors and understanding their action ...
Researchers first injected transgenic mice expressing human IAPP with preformed fibrils of synthetic IAPP, proIAPP, or beta-amyloid. After 10 months on a high-fat diet, tissue was analyzed using an amyloid-specific dye. The number of islets with amyloid was significantly increased compared to controls by all three types of fibrils, and the amyloid consisted of IAPP in all groups. No amyloid deposits were found in the spleen, kidney, liver, heart, or lungs. The results demonstrate for the first time that fibril injections could seed amyloid formation in the pancreas and also that brain amyloid could cross-seed fibril formation in the pancreas.. In subsequent experiments the investigators analyzed human tissues from the pancreas and brain. Using antibody-based methods, they found that pancreas sections with islet amyloid from patients diagnosed with T2D showed no beta-amyloid immunoreactivity, whereas all samples were immunoreactive for IAPP.. To further investigate whether IAPP and beta-amyloid ...
Misfolding and aggregation of normally soluble proteins into amyloid fibrils and their deposition and accumulation underlies a variety of clinically significant diseases. Fibrillar aggregates with amyloid-like properties can also be generated in vitro from pure proteins and peptides, including those not known to be associated with amyloidosis. Whereas biophysical studies of amyloid-like fibrils formed in vitro have provided important insights into the molecular mechanisms of amyloid generation and the structural properties of the fibrils formed, amyloidogenic proteins are typically exposed to mild or more extreme denaturing conditions to induce rapid fibril formation in vitro. Whether the structure of the resulting assemblies is representative of their natural in vivo counterparts, thus, remains a fundamental unresolved issue. Here we show using Fourier transform infrared spectroscopy that amyloid-like fibrils formed in vitro from natively folded or unfolded β2-microglobulin (the protein ...
In this study, we have found that the major protein component of the B. subtilis biofilm matrix, TasA, forms amyloid fibers. Amyloid fibers have been extensively studied in human neurodegenerative diseases including Alzheimers and Parkinsons or spongiform encephalopathies induced by prions (15, 36, 37). Besides having a role in pathogenicity, amyloids may also be an important factor in the physiology of the diverse organisms. For example, amyloids contribute to the attachment of bacteria to surfaces and the raising of aerial structures (18, 19), and they have a role in pathogenic processes such as adhesion to host cells (7, 10, 38) and induction of toxicity to host cells (16). However, in biofilm formation, only curli amyloid fibers of E. coli have been studied in detail (10). TasA is an amyloid protein shown to be specifically involved in the formation of a biofilm matrix by a Gram-positive organism. Now that two model systems that use amyloids to help structure their biofilms have been ...
Amyloidosis is a protein conformational disorder in which amyloid fibrils accumulate in the extracellular space and induce organ dysfunction. Recently, two different amyloidogenic proteins, transthyretin (TTR) and apolipoprotein A-I (Apo A-I), were identified in amyloid deposits in knee joints in patients with knee osteoarthritis (OA). However, clinicopathological differences related to those two kinds of amyloid deposits in the knee joint remain to be clarified. Here, we investigated the clinicopathological features related to these knee amyloid deposits associated with knee OA and the biochemical characteristics of the amyloid deposits. We found that all of our patients with knee OA had amyloid deposits in the knee joints, especially in the meniscus, and those deposits were primarily derived from TTR and/or Apo A-I. Some patients with knee OA, however, had unclassified amyloid deposits. One of our interesting observations concerned the different effects of aging on each type of amyloid formed. ...
BACKGROUND: The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimers disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon-prostate tissue remodelling in middle-aged and elderly men. METHODOLOGY/PRINCIPAL FINDINGS: By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This ...
Localized amyloid deposition is known to occur commonly in the articular cartilage of elderly patients. Its pathogenesis is uncertain and it is not known if other cartilage-containing tissues also contain amyloid deposits. Systemic amyloid deposits are known to contain highly sulphated glycosaminoglycans, a major constituent of cartilage. As the composition of articular cartilage glycosaminoglycans is known to change with age, we sought to identify whether localized amyloid deposition in cartilage was glycosaminoglycan-related. We examined specimens of articular cartilage over a wide age range and also examined a variety of cartilaginous tumours and tumour-like lesions for the presence or absence of amyloid deposits. Using mucin histochemistry (alcian blue: MgCl2 critical electrolyte concentration) and immunohistochemistry, we found that highly sulphated glycosaminoglycans (0.9 M and 1 M MgCl2), in particular keratan sulphate, localized to amyloid deposits in both articular cartilage and loose bodies
It has long been understood that amyloids can be lethal in systemic diseases. More recently, it has been accepted that local cerebral aggregation of the small peptide A beta is involved in the pathogenesis of Alzheimers disease. Protein aggregation, with the generation of small amyloid deposits in specific organs, also occurs outside the central nervous system and often is associated with increased cell death. In this review, we discuss two lesser known but common localized amyloid fibril-forming proteins: the polypeptide hormone islet amyloid polypeptide (IAPP) and the lactadherin-derived peptide medin. IAPP aggregates and induces the depletion of islet beta-cells in type 2 diabetes and in islets transplanted into type 1 diabetic subjects. Initial amyloid deposition occurs intracellularly and parts of this amyloid consist of proIAPP. Medin derived from lactadherin expressed by smooth muscle cells aggregates into amyloid in certain arteries, particularly the thoracic aortic media layer, and may ...
Amyloid accumulation in the brain of Alzheimers patients results from altered processing of the 39- to 43-amino acid amyloid protein (A). [1], [2]. The excessive accumulation of A peptides in AD may be due to enhanced endoproteolytic cleavage of membrane bound amyloid precursor protein (APP), over-expression of APP and/or decreased clearance of A from the central nervous system (CNS) [3]C[5]. Postmortem analyses of AD subjects reveal that amyloid plaques in the brain suffuse vascular cells in addition to the parenchymal. The ramifications of this vascular infiltration for AD has been less well analyzed than the parenchymal A, but has generated 61939-05-7 manufacture considerable interest with studies that -amyloid fibrils accumulate in small blood vessels, capillary vessels and arterioles of Rabbit Polyclonal to PRKY the human brain [6]C[8]. Cerebrovascular amyloid toxicity generally manifests itself in the break of the blood-brain-barrier and improved irritation in the cerebrovasculature [9], ...
In this study, we have compared the biological effects of different Aβ assemblies on primary mixed brain cultures to determine whether nonfibrillar or immature, prefibrillar forms of Aβ may be neurotoxic. This potentially important source of neuronal injury has been overlooked until very recently, perhaps because the neuropathological diagnosis of AD requires the presence of abundant fibrillar amyloid in the form of myriad neuritic plaques in postmortem brain tissue. Because mature amyloid plaques surrounded by dystrophic neurites, activated microglia, and reactive astrocytes are composed principally of Aβ fibrils, it has been generally assumed that fibrillar Aβ is the form most likely to be responsible for neuronal and glial injury in AD. The apparent importance of amyloid fibrils has been reinforced by cell culture studies that consistently show that the aggregation state of Aβ, most notably the formation of amyloid fibrils, is associated with neuronal alteration and loss (Pike et al., ...
Since 1998, a great deal of progress has been made towards determining and understanding the molecular structures of amyloid fibrils, including fibrils formed by the β-amyloid peptide that is...
Actually, the photo depicts amyloid plaques, a frequent topic in the context of Alzheimers disease. Pathologist William Lewis photo reminds us that amyloid can also appear in the heart.. Amyloidosis of the heart is a set of complex diseases caused by the accumulation of cellular proteins that form an amyloid plaque. Although http://www.oakleyonorder.com/ amyloidosis was described more than 100 years ago, the causative proteins were not identified until recent chemical analyses were conducted. This image shows an amyloid plaque stained with Congo red stain and viewed through a polarized lens. The optical properties of the amyloid-forming protein cause it to appear green, while other matrix materials within the plaque appear as orange and blue.. The photo, which was one of the winners of the FASEB (Federation of American Societies for Experimental Biology) 2013 BioArt competition, was featured on NIH director Francis Collins blog this week.. Lewis, who studies the effects of antiretroviral ...
We report on the photophysical and optical properties of a polyfluorene derivative (PFO) and its binding to the amyloid-forming protein insulin. The complexation is based on weak supramolecular interactions between amyloid fibrils and PFO in dissolved and aggregated forms. In particular, complexes of polyflu
Background The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimers disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon - prostate tissue remodelling in middle-aged and elderly men.. Methodology/Principal Findings By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This ...
A five-year trial at a Brisbane Hospital has increased the accuracy of diagnosing patients with amyloidosis, a group of rare and incurable diseases caused by abnormal protein deposits in tissues and organs.. Researchers from The University of Queensland and the Princess Alexandra Hospital Amyloidosis Centre used a new test to identify the specific protein that caused the damage in each patient.. Associate Professor Michelle Hill from the UQ Diamantina Institute said different amyloid conditions had different protein culprits, and required different treatments.. For instance, in one type of amyloidosis known as AL, chemotherapy is required, but chemo is inappropriate and potentially harmful to patients with other amyloid conditions, Dr Hill said.. In the trial we used cutting-edge techniques including laser-capture microdissection and tandem mass spectrometry to identify proteins in the amyloid deposits.. This technique was recently reported by the Mayo Clinic in the United States as a new ...
Protein misfolding and aggregation cause serious degenerative conditions such as Alzheimers, Parkinson, and prion diseases. Damage to membranes is thought to be one of the mechanisms underlying cellular toxicity of a range of amyloid assemblies. Previous studies have indicated that amyloid fibrils can cause membrane leakage and elicit cellular damage, and these effects are enhanced by fragmentation of the fibrils. Here we report direct 3D visualization of membrane damage by specific interactions of a lipid bilayer with amyloid-like fibrils formed in vitro from β2-microglobulin (β2m). Using cryoelectron tomography, we demonstrate that fragmented β2m amyloid fibrils interact strongly with liposomes and cause distortions to the membranes. The normally spherical liposomes form pointed teardrop-like shapes with the fibril ends seen in proximity to the pointed regions on the membranes. Moreover, the tomograms indicated that the fibrils extract lipid from the membranes at these points of distortion ...
This presentation is on the effects of sleep deprivation on β-amyloid accumulation in the brain. During sleep, the glymphatic system is involved in the clearance of metabolic including metabolic wastes. β-amyloid accumulation is directly correlated to impairment of brain function and Alzheimers disease. Increased sleep or ways to decrease β-amyloid accumulation could be beneficial in the prevention of Alzheimers. Data collected in the article published by Shokri-Kojori, E. et al. suggests that sleep deprivation negatively affected mood and was correlated with increases in amyloid- β burden in the right hippocampal cluster. Further research on how sleep impacts β-amyloid accumulation should be conducted.
Recently, we have performed super-resolution imaging of fluorescently-stained amyloid fibrils derived from the low pH form of β2-microglobulin that is known to be associated with dialysis-related amyloidosis [43]. In our NSOM experiments, we used Nile Red as the fluorescent marker rather than more commonly used ThT due to the following reasons: (i) ThT has also been shown to bind to amorphous protein aggregates owing to the presence of inherent charge [44], (ii) ThT assay at neutral pH cannot be performed to detect amyloid fibrils that are formed at low pH and disintegrate at neutral pH [45], (iii) the low quantum yield of ThT prevents it from being utilized in single-molecule/particle imaging experiments [46] and (iv) ThT exhibits an emission maximum at ~482 nm upon binding to amyloid fibrils and hence, commonly used laser lines such as 488 and 532 nm cannot be used as excitation wavelengths. All these problems can be circumvented if Nile Red is used [47]. Hence, Nile Red was added into the ...
Alzheon presents ALZ-801 data in oral session on the role of amyloid oligomers in Alzheimers Disease 10th Clinical Trials on Alzheimers Disease mtg.
The lack of understanding of amyloid fibril formation at the molecular level is a major obstacle in devising strategies to interfere with the pathologies
Amyloid fibrils connected with Alzheimers disease and an array of various other neurodegenerative diseases possess a cross -sheet structure where primary chain hydrogen bonding occurs between -strands in direction of the fibril axis. A fibrils as assayed by thioflavin T fluorescence, electron microscopy and solid-state NMR spectroscopy. The alternating huge and little amino acids within the GxFxGxF series are complementary towards the corresponding proteins within the IxGxMxG theme within BIBW2992 the C-terminal series of A40 and A42. Significantly, the designed peptide inhibitors considerably decrease the toxicity induced by A42 on cultured rat cortical neurons. isnt crucial for stabilizing sheet-to-sheet packaging in amyloid fibrils. The incident of glycine by itself or in various other motifs within -bed sheets is sufficient to generate the corrugated surface area if the average person -strands possess a parallel, in-register orientation. For instance, -synuclein, the proteins connected with ...
Since its founding in 2003, Kinexis Inc. has pursued several lead development programs, including prokineticin receptor modulators and melanin concentrating hormone (MCH)-1 receptor antagonists. But the San Diego-based companys third lead program - licensed from the University of California at Irvine in 2004 - turned out to be the charm. The program was built around a platform to generate antibodies targeting oligomeric conformations of amyloid proteins, which form the hallmark plaques of Alzheimers disease. And in 2006, the amyloid oligomer program officially became Kinexiss primary focus at the urging of new CEO Kevin Anderson.
Background. Liver transplantation (LTx) is an accepted treatment for hereditary transthyretin (TTR) amyloidosis (ATTR). However, unforeseen heart complications, especially a rapid development of cardiomyopathy after LTx has affected mortality and morbidity. Recently, a relationship between ATTR-fibril composition and cardiomyopathy has been noted. The aim of this study was to investigate whether development of cardiomyopathy and heart failure in LTx ATTR amyloid patients is related to amyloid fibril composition.. Methods. Twenty-four patients with hereditary ATTR amyloidosis who had undergone LTx and have had their amyloid fibril type tested were available for the study. They had been examined by echocardiography including tissue Doppler and speckle tracking echocardiography before and after LTx. Patients were divided into two groups according to fibril composition, 10 patients with type A fibrils (a mixture of truncated and full-length TTR) and 14 patients with type B fibrils (full-length TTR ...
Andreas Bäumler. The protein forming plaques in Alzheimers patients is normally soluble. When the protein folds improperly, it forms amyloid deposits that are associated with brain inflammation. Until now, scientists have not been able to identify what causes this destructive, chronic inflammation.. Bäumler and his colleagues did not expect to be studying Alzheimers disease. They were studying inflammation of the gut caused by bacteria when they discovered that the innate immune system was being triggered by a structural feature of bacterial amyloids and not by the amino acids that make up the proteins in the biofilms.. When we destroyed the ability of the proteins to aggregate, we no longer saw the same immune response, Bäumler said.. When the researchers figured out the amyloid structure was responsible for triggering the immune system, they decided to see whether the same immune response was being triggered by structurally identical amyloids associated with human disease. They chose to ...
While striatal amyloid may mark the late preclinical phase, Sebastian Palmqvist of Lund University, Sweden, made a case for CSF Aβ42 being one of the earliest preclinical markers of AD. Levels of this fluid biomarker drop as amyloid plaques accumulate in the brain, and this becomes apparent before amyloid PET scans turn positive, Palmqvist claimed. Previous cross-sectional studies had hinted at this, with some participants having low CSF Aβ42 in the absence of an amyloid PET signal, but it was unclear if all of these PET-negative individuals were on track for AD (see Fagan et al., 2009; Mattsson et al., 2015). Confusing matters further, at least one study reported finding a few people with positive amyloid scans and normal CSF Aβ42 (see Landau et al., 2013). To observe the relationship of the two markers over time, Palmqvist and colleagues Niklas Mattsson and Oskar Hansson at Lund stratified 437 ADNI 2 participants according to whether they were positive or negative on each. For brain ...
In this work, α-synuclein amyloid fibrils—the formation of which is a biomarker of Parkinson’s disease—were investigated using the fluorescent probe thioflavin T (ThT). The experimental conditions of protein fibrillogenesis were chosen so that a sufficient number of continuous measurements could be performed to characterize and analyze all stages of this process. The reproducibility of fibrillogenesis and the structure of the obtained aggregates (which is a critical point for further investigation) were proven using a wide range of physical-chemical methods. For the determination of ThT-α-synuclein amyloid fibril binding parameters, the sample and reference solutions were prepared using equilibrium microdialysis. By utilizing absorption spectroscopy of these solutions, the ThT-fibrils binding mode with a binding constant of about 104 M−1 and stoichiometry of ThT per protein molecule of about 1:8 was observed. Fluorescence spectroscopy of the same solutions with the
Because many types of bacteria depend on amyloid-rich curli to stick to host surfaces, disrupting these structures might open a new avenue for combating biofilms. Amyloid structures, which consist of aggregated fibers of insoluble protein in web-like sheets, are a substantial part of what makes curli so good at this task. Moreover, in addition to enhancing how well cells stick to surfaces, the aggregated fibers within curli help them to resist heat and chemical damage. More and more microbiologists admit to being intrigued by amyloid structures.
The generation and assembly of Aβ peptides into pathological aggregates is associated with neurodegenerative diseases including Alzheimers disease. Goal of this project was to better understand the dynamics of γ-secretase a key enzyme for the formation of Aβ peptides using large scale Molecular Dynamics simulations and how it associates with substrate molecules. Using the HPC system SuperMUC it was possible to characterize local and global motions of γ-secretase in atomic detail and how it is related to function. In addition, large scale simulations were employed to investigate the amyloid propagation mechanism at the tip of an already formed amyloid fragment. The kinetics and thermodynamics of the process were analyzed and compared to alternative amyloid secondary nucleation events.
DNA sequences encoding β-amyloid-related proteins associated with Alzheimers disease are disclosed. Also provided herein is a DNA sequence encoding a novel protease inhibitor. These sequences are used in producing or constructing recombinant β-amyloid core protein, β-amyloid-related proteins and recombinant or synthetic immunogenic peptides. Antibodies generated against the recombinant proteins or immunogenic peptides derived therefrom can be used for cerebral fluid or serum protein diagnosis of Alzheimers disease.
Amyloid oligomers are nonfibrillar polypeptide aggregates linked to diseases, such as Alzheimers and Parkinsons. Here we show that these aggregates possess a compact, quasi-crystalline architect ...
A few months ago, experts were talking about the next generation of disease-modifying drugs that were expected to help treat Alzheimers disease by attacking amyloid plaque in the brain. In fact, they were arguing that any newly written treatment guidelines were likely to be quickly outdated by the advent of new, powerful drugs. Drug companies were also optimistic, developing all kinds of anti-amyloid drugs that were expected to fundamentally alter the course of the disease.. Amyloid is the stuff that gets in the brain in Alzheimers disease. The theory is that amyloid is toxic to the brain, setting up the slow burn we know as Alzheimers disease. Based on that theory, weve assumed that drugs that prevent amyloid from developing, or that promote its removal, are drugs that would be good for treating Alzheimers.. So the scientists of the world attacked amyloid with a vengeance, generating drugs to clamp down on the enzyme that produces it, on the process that causes it to crystallize in ...
Background:. Alzheimers dementia (AD) is a common disorder of the aging brain causing progressive and irreversible impairment in memory and cognitive function. Beginning with the initial description of Alzheimers dementia (AD) in 1906 when abnormal accumulations of plaques and tangles in the brain of a woman with severe cognitive impairment were first noted, the pathophysiology of AD has been intimately associated with a progressive neuropathologic process involving abnormal protein deposition in brain. More recent work has implicated the accumulation of β-amyloid as an early feature of AD, which may be directly responsible for some of the clinical manifestations of the disease. Pathologic studies suggest levels of β-amyloid are elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases in amyloid are strongly correlated with cognitive decline. Increases in β-amyloid precede significant tau pathology suggesting the formation of plaques early in the ...
Alzheimers disease (AD) and familial Danish dementia (FDD) are degenerative neurological diseases characterized by amyloid pathology. Normal human sera contain IgG antibodies that specifically bind diverse preamyloid and amyloid proteins and have shown therapeutic potential in vitro and in vivo. We cloned one of these antibodies, 3H3, from memory B cells of a healthy individual using a hybridoma method. 3H3 is an affinity-matured IgG that binds a pan-amyloid epitope, recognizing both Aβ and λ Ig light chain (LC) amyloids, which are associated with AD and primary amyloidosis, respectively. The pan-amyloid-binding properties of 3H3 were demonstrated using ELISA, immunohistochemical studies, and competition binding assays. Functional studies showed that 3H3 inhibits both Aβ and LC amyloid formation in vitro and abrogates disruption of hippocampal synaptic plasticity by AD-patient-derived soluble Aβ in vivo. A 3H3 single-chain variable fragment (scFv) retained the binding specificity of the 3H3 IgG and
Extracellular Curli formation by bacteria together with the intralumenal formation of pMel17 Mα fibrous striations by mammalian cells demonstrate that amyloid-like fibrils can be a natural product-a quaternary protein nanostructure formed by biological systems. The fact that mammalian cells utilize a fibril structure to mediate function emphasizes that tuning of protein structure by proteolysis can be a very powerful determinant for expanding the biological diversity of polypeptides. It is apparent that E. coli and Salmonella go to great lengths to control amyloidogenesis, as evidenced by the dedication of at least two operons to harness the potential of the amyloid quaternary structure to perform a useful biological function, and to prevent misassembly elsewhere in the cell. It is almost certain that numerous mammalian genes are also used to control amyloid-like fibril formation within organelles such as the melanosome to allow to its potential to be recognized. Interestingly, the process of ...
Researchers find fluorodeoxyglucose (FDG) PET is a better indicator of cognitive performance for patients with Alzheimers disease, mild cognitive impairment, when compared to PET scans that detect amyloid protein. Philadelphia, PA, USA - While the presence of beta-amyloid plaques in the brain may be a hallmark of Alzheimers disease, giving patients an amyloid PET scan is not an effective method for measuring their cognitive function, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Thomas Jefferson University. The researchers concluded that fluorodeoxyglucose (FDG) PET, which measures the brains glucose consumption as a marker of neural activity, is a stronger approach for assessing the progression and severity of Alzheimers and mild cognitive impairment (MCI) as compared to florbetapir-PET scans, which reveal amyloid protein deposits in the brain. This suggests that FDG-PET is also a better means for determining the ...
The β-amyloid peptide (Aβ) may be the major constituent from the amyloid core of senile plaques within the mind of patients with Alzheimers disease (AD). resulted in a drastic reduced amount of Aβ42 and Aβ40 secretion. β-Cleavage of mutant APP HOE 32021 had not been inhibited and reduced amount of Aβ secretion resulted from inhibition of γ-cleavage. It had been anticipated that reduced γ-cleavage of mutant APP would derive from inhibition of its dimerization. Amazingly mutations from the GxxxG theme actually improved dimerization from the APP C-terminal fragments perhaps with a different TM α-helical user interface. Increased dimerization from the TM APP C-terminal area did not have an effect on AICD creation. These results obviously demonstrate that both orientation and dimerization from the APP TM area differently have an effect on Aβ and AICD creation. The intensifying deposition of β-amyloid peptide (Aβ)1 resulting in the forming of senile plaques can be an invariant feature of ...
(Phys.org)-Several fatal brain disorders, including Parkinsons disease, are connected by the misfolding of specific proteins into disordered clumps and stable, insoluble fibrils called amyloid. Amyloid fibrils are hard ...
Alzheimers disease is the leading cause of late-life dementia. An increasing body of evidence has linked assemblies of a common peptide, the amyloid protein, to the disease. While plaques formed from large assemblies of this protein are known to be the eventual result of Alzheimers, recent evidence suggests that small assemblies - or oligomers - of amyloid are the toxic agents responsible for the disease symptoms.. In this research, scientists used mass spectrometry to study the mixture of oligomers formed by the amyloid 42 protein. While many types of amyloid assemblies have been described, the researchers found that oligomers made up of 12 units of amyloid 42 appear to be a key neurotoxic agent in the development of Alzheimers.. ...
Since the beginning of the years 2000, more and more examples of functional amyloid fibers have been discovered in bacteria and fungi as well as in the mammals realm[1-2]. Very recently, a study on about forty peptide hormones has demonstrated that those were stored inside pituitary secretory granules under the form of amyloid fibers[3]. Beyond the structural biology question, we are especially interested in these molecules because we think they might be appropriate models to tackle broader issues like biomimetic self-assembly and amyloid formation - amyloid understood as
Since the beginning of the years 2000, more and more examples of functional amyloid fibers have been discovered in bacteria and fungi as well as in the mammals realm[1-2]. Very recently, a study on about forty peptide hormones has demonstrated that those were stored inside pituitary secretory granules under the form of amyloid fibers[3]. Beyond the structural biology question, we are especially interested in these molecules because we think they might be appropriate models to tackle broader issues like biomimetic self-assembly and amyloid formation - amyloid understood as
en] Amyloidogenic model peptides are invaluable for investigating assembly mechanisms in disease related amyloids and in protein folding. During aggregation, such peptides can undergo bifurcation leading to fibrils or crystals, however the mechanisms of fibril-to-crystal conversion are unclear. We navigate herein the energy landscape of amyloidogenic peptides by studying a homologous series of hexapeptides found in animal, human and disease related proteins. We observe fibril-to-crystal conversion occurring within single aggregates via untwisting of twisted ribbon fibrils possessing saddle-like curvature and cross-sectional aspect ratios approaching unity. Changing sequence, pH or concentration shifts the growth towards larger aspect ratio species assembling into stable helical ribbons possessing mean-curvature. By comparing atomistic calculations of desolvation energies for association of peptides we parameterise a kinetic model, providing a physical explanation of fibril-to-crystal ...
Westwell-Roper, C.Y.; Chehroudi, C.A.; Denroche, H.C.; Courtade, J.A.; Ehses, J.A.; Verchere, C.Bruce., 2015: IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice
Human islet amyloid polypeptide (hIAPP) accumulates as pancreatic amyloid in type 2 diabetes and readily forms fibrils in vitro. Investigations into the mechanism of hIAPP fibril formation have focused largely on residues 20 to 29, which are considered to comprise a primary amyloidogenic domain. In …
Islet amyloid is the most common characteristic feature of the islets in type 2 diabetes, being found in up to 90% of diabetic patients at post-mortem. lt has as its unique component the islet beta-cell peptide islet amyloid polypeptide (IAPP), which is eo-secreted with insulin. Because all human subjects produce and secrete the amyloidogenic form of IAPP, yet not all develop islet amyloid, some other factors must be involved in islet amyloid formation. The aim of the research presented in this thesis was to study factors of importance for the IAPP amyloidogenesis in type 2 diabetes. We developed a mouse monoclonal antibody to raVmouse IAPP (MAb4A5). MAb4A5 shows reactivity with IAPP in different species without detecting its close relative CGRP. In the pancreatic islets from patients with type 2 diabetes and diabetic cat, MAb4A5 labels immunohistochemically cellular IAPP but not IAPP in islet amyloid deposits. In contrast to MAb4A5 polyclonal rabbitiAPP antisera label beta cells close to ...
2019) Nucleation of β-rich oligomers and β-barrels in the early aggregation of human islet amyloid polypeptide. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1865 (2). pp. 434-444 ...
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Our primary objective was to establish whether metformin or sitagliptin alone and in combination favorably modified disease progression in the HIP rat model of type 2 diabetes. Although loss of β-cell mass in the HIP rat was slowed by this combination therapy, unexpected adverse actions on the exocrine pancreas were also observed.. Metformin has been shown to delay type 2 diabetes onset in humans (13). Because enhanced insulin sensitivity through lifestyle changes also delays diabetes (13), at least part of the protective effect of metformin may be mediated by metformins actions to enhance hepatic insulin sensitivity through its actions on AMP-activated kinase (33). Metformin decreased β-cell apoptosis in isolated human islets from patients with type 2 diabetes (34). In the current study, metformin was more effective than sitagliptin in reducing β-cell apoptosis in the high-fat diet -fed HIP rat. Although sitagliptin alone also suppressed β-cell apoptosis, there was no added benefit of ...
Amyloidosis is caused by deposition in tissues of abnormal protein in a characteristic fibrillar form. There are many types of amyloidosis, classified according to the soluble protein precursor from which the amyloid fibrils are derived. Accurate identification of amyloid type is critical in every case since therapy for systemic amyloidosis is type specific. In ∼20-25% cases, however, immunohistochemistry (IHC) fails to prove the amyloid type and further tests are required. Laser microdissection and mass spectrometry (LDMS) is a powerful tool for identifying proteins from formalin-fixed paraffin-embedded tissues. We undertook a blinded comparison of IHC, performed at the UK National Amyloidosis Centre, and LDMS, performed at the Mayo Clinic, in 142 consecutive biopsy specimens from 38 different tissue types. There was 100% concordance between positive IHC and LDMS, and the latter increased diagnostic accuracy from 76% to 94%. LDMS in expert hands is a valuable tool for amyloid ...
Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a cross-beta x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common beta-sheet core structure, they display a substantial degree of morphological variation. One striking example is the remarkable ability of human apolipoprotein C-II amyloid fibrils to circularize and form closed rings. Here we explore in detail the structure of apoC-II amyloid fibrils using electron microscopy, atomic force microscopy, and x-ray diffraction studies. Our results suggest a model for apoC-II fibrils as ribbons approximately 2.1-nm thick and 13-nm wide with a helical repeat distance of 53 nm +/- 12 nm. We propose that the ribbons are highly flexible with a persistence length of 36 nm. We use these observed biophysical properties to model the apoC-II amyloid fibrils either as wormlike chains or using a random-walk approach, and confirm that the probability of ring
TY - JOUR. T1 - Identification and characterization of amyloid protein AA in spontaneous canine amyloidosis. AU - Benson, M. D.. AU - Dwulet, F. E.. AU - DiBartola, S. P.. PY - 1985/1/1. Y1 - 1985/1/1. N2 - Amyloid fibrils were isolated from kidney tissue of a dog that presented with renal failure due to spontaneous amyloidosis. This fibril material was reduced, alkylated and chromatographed on a column of Sepharose CL6B. A major retarded fraction, when subjected to amino acid sequencing, demonstrated a blocked amino terminus. The isolated protein was then degraded with cyanogen bromide, and the resultant three peptides were isolated by high-pressure liquid chromatography. The amino acid sequence of one peptide corresponded to the sequence of human amyloid protein AA from position 17 to 23. A second peptide gave an animo acid sequence homologous to the published human protein AA sequence starting with position 24. Although a high degree of homology between canine and human AA is seen, the ...
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Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are rare genetic causes of familial Alzheimers disease (AD). A mutation at codon 693 of APP has also been described as the genetic defect in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a APP692Ala--|Gly (Flemish) mutation as a cause of intracerebral hemorrhage and presenile dementia diagnosed as probable AD in a Dutch family. We now describe the post-mortem examination of two demented patients with the APP692 mutation. The neuropathological findings support the diagnosis of AD. Leptomeningial and parenchymal vessels showed extensive deposition of Abeta amyloid protein. Numerous senile plaques consisted of large Abeta amyloid cores, often measuring more than 30 microm in diameter and were surrounded by a fine meshwork of dystrophic neurites. In addition, there were a large number of paired helical filaments in pyramidal neurons and dystrophic neurites. Our findings show that the
This study describes a technique which makes it possible to introduce the amyloid-like order to protein aggregates by using the scaffolding framework built from supramolecular, fibrillar Congo red structures arranged in an electric field. The electric field was used not only to obtain a uniform orientation of the charged dye fibrils, but also to make the fibrils long, compact and rigid due to the delocalization of pi electrons, which favors ring stacking and, as a consequence, results in an increased tendency to self-assemble. The protein molecules (immunoglobulin L chain lambda, ferritin) attached to this easily adsorbing dye framework assume its ordered structure. The complex precipitating as plate-like fragments shows birefringence in polarized light. The parallel organization of fibrils can be observed with an electron microscope. The dye framework may be removed via reduction with sodium dithionite, leaving the aggregated protein molecules in the ordered state, as confirmed by X-ray ...
Islet Amyloid Polypeptide (Amylin or Diabetes Associated Peptide or Insulinoma Amyloid Peptide or IAPP - Market Research Reports and Industry Analysis
Opening of K(ATP)-channels reduces beta-cell vulnerability to apoptosis induced by h-IAPP oligomers. This effect is not due to a direct interaction of K(ATP)CO with h-IAPP, but might be mediated through hyperpolarization of the beta-cell membrane induced by opening of K(ATP)-channels. Induction of b …
We have produced a panel of 32 unique monoclonal antibodies that recognize common structural elements in amyloid aggregates, like the alpha-synuclein aggregates that are believed to play an important role in PD pathogenesis. Although these antibodies were originally produced against Abeta amyloid from Alzheimer s disease, we found that many of them recognize common or generic epitopes (or antibody binding sites) that occur on amyloid aggregates from a number of different amyloids made from different protein sequences. For some of these antibodies, we have already shown that interact with alpha-synuclein aggregates in vitro. In this project, we will test the immunoreactivity of all of the antibodies against alpha-synuclein oligomers and fibrils. We will also test whether any of the antibodies can detect pathological oligomers in human PD brain. Antibodies that react with pathological amyloid aggregates in brain would represent candidates for therapeutic development.. Relevance to ...
Protein misfolding and aggregation are thought to underlie the pathogenesis of many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a stepwise protein misfolding process begins with the conversion of soluble protein monomers to prefibrillar oligomers and progresses to the formation of insoluble amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in eyes afflicted with age-related macular degeneration (AMD). Recent characterizations of drusen have revealed protein components that are shared with amyloid deposits. However, characteristic amyloid fibrils have thus far not been identified in drusen. In this study, we tested the hypothesis that nonfibrillar oligomers may be a common link in amyloid diseases. Oligomers consisting of distinct amyloidogenic proteins and peptides can be detected by a recently developed antibody that is thought to recognize a common structure. Notably, oligomers exhibit cellular toxicity, which suggests that they play a role in ...
The L55P transthyretin (TTR) familial amyloid polyneuropathy-associated variant is distinct from the other TTR variants studied to date and the wild-type protein in that the L55P tetramer can dissociate to the monomeric amyloidogenic intermediate and form fibril precursors under physiological conditions (pH 7.0, 37 degrees C). The activation barrier associated with L55P-TTR tetramer dissociation is lower than the barrier for wild-type transthyretin dissociation, which does not form fibrils under physiological conditions. The L55P-TTR tetramer is also very sensitive to acidic conditions, readily dissociating to form the monomeric amyloidogenic intermediate between pH 5.5-5.0 where the wild-type TTR adopts a nonamyloidogenic tetrameric structure. The formation of the L55P monomeric amyloidogenic intermediate involves subtle tertiary structural changes within the beta-sheet rich subunit as discerned from Trp fluorescence, circular dichroism analysis, and ANS binding studies. The assembly of the ...
Amyloid diseases in man are caused by as many as 23 different pre-cursor proteins already described. Cardiologists predominantly encounter three main types of amyloidosis that affect the heart: light chain (AL) amyloidosis, senile systemic amyloidosis (SSA) and hereditary amyloidosis, most commonly caused by a mutant form of transthyretin. In the third world, secondary amyloid (AA) is more prevalent, due to chronic infections and inadequately treated inflammatory conditions. Much less common, are the non-transthyretin variants, including mutations of fibrinogen, the apolipoproteins apoA1 and apoA2 and gelsolin. These rarer types do not usually cause significant cardiac compromise. Occurring worldwide, later in life and of less clinical significance, isolated atrial amyloid (IAA) also involves the heart. Heart involvement by amyloid often has devastating consequences. Clinical outcome depends on amyloid type, the extent of systemic involvement and the treatment options available. An exact ...
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Several studies have indicated that certain misfolded amyloids composed of tau, β-amyloid or α-synuclein can be transferred from cell to cell, suggesting the contribution of mechanisms reminiscent of those by which infective prions spread through the brain. This process of a prion-like spreading between cells is also relevant as a novel putative therapeutic target that could block the spreading of proteinaceous aggregates throughout the brain which may underlie the progressive nature of neurodegenerative diseases. The relevance of β-amyloid oligomers and cellular prion protein (PrPC) binding has been a focus of interest in Alzheimers disease (AD). At the molecular level, β-amyloid/PrPC interaction takes place in two differently charged clusters of PrPC. In addition to β-amyloid, participation of PrPC in α-synuclein binding and brain spreading also appears to be relevant in α-synucleopathies. This review summarizes current knowledge about PrPC as a putative receptor for amyloid proteins ...
The misfolding and aggregation of amyloid β (1-42) peptide is crucial for a mechanical understanding of the formation of Alzheimers disease. To investigate the detailed aggregation pathway and mechanism, it is important to identify the secondary structures of different aggregation forms. Here, we report probing different amyloid β aggregations in real time by using correlated approaches such as shell-isolated surface-enhanced Raman spectroscopy, thioflavin T fluorescence assay, and atomic force microscopy imaging. Our experimental results of Raman shifts have been further demonstrated by theoretical calculation, which indicates that the Raman spectral fingerprint changes are originated from the amyloid β secondary structure changes. Copyright © 2013 John Wiley & Sons, Ltd. ...
The review summarizes research into the highly relevant topics of cholinesterase and amyloid aggregation inhibitors connected to tacrine congeners, both of which are associated with neurogenerative diseases. Various opinions will be discussed regarding the dual binding site inhibitors which are characterized by increased inhibitor potency against acetylcholin/butyrylcholine esterase and amyloid formation. It is suggested that these compounds can both raise levels of acetylcholine by binding to the active site, and also prevent amyloid aggregation. In connection with this problem, the mono/dual binding of the multifunctional derivatives of tacrine, their mode of action and their neuroprotective activities are reported. The influence of low molecular compounds on protein amyloid aggregation, which might be considered as a potential therapeutic strategy in the treatment of Alzheimers disease is also reported. Finally, attention is paid to some physico-chemical factors, such as desolvation energies
A pathologic feature of type 2 diabetes is the presence of islet amyloid deposits composed predominantly of amylin (1). Whether islet amyloid is merely a marker of type 2 diabetes or actually contributes to the disease is a matter of some discussion. Several lines of evidence suggest an association between the presence of islet amyloid and diabetes and reduced β-cell mass. In monkeys, the formation of islet amyloid correlates with early reduced insulin secretion and glucose intolerance, and, with time, correlates with greater deficiency in insulin secretion and glucose tolerance and ultimately hyperglycemia (22). In humans, the degree of amyloid formation correlates with the severity of diabetes, as evidenced by the requirement for insulin replacement therapy (23,24). Other evidence suggests that β-cell death is caused by intermediate-sized fibrils that are precursors of islet amyloid (3,4). In this case, islet amyloid deposits reflect an end-stage effect of amylin aggregation secondary to ...
Alzheimers disease (AD) is a fatal neurodegenerative disease, and is the most common form of dementia, affecting 1-2% of the population in industrialized countries. It is believed that intermediate species formed during amyloid Bpeptide (AB) polymerization play a key role in the pathogenesis of AD, but it is not known how such toxic effects are exerted. A detailed model of the initial aggregation of AB, as well as the structure of amyloid fibrils, is a significant goal for the understanding of the molecular mechanisms behind Alzheimers disease. The aim of this thesis was to )study AB polymerization and interaction with cell membranes using fluorescence correlation spectroscopy (FCS). )Utilizing the high sensitivity of FCS for developing a method for detecting and counting single AB aggregates in cerebrospinal fluid (CSF) from AD patients and controls. )Delineating the minimum structural requirements for amyloid fibril formation in general and assessing the alignment of strands within ...
Synonyms for amyloid plaque in Free Thesaurus. Antonyms for amyloid plaque. 1 synonym for amyloid plaque: amyloid protein plaque. What are synonyms for amyloid plaque?
Amyloids - clumps of misfolded proteins found in the brains of people with Alzheimers disease and other neurodegenerative disorders - are the quintessential bad boys of neurobiology. Theyre thought to muck up the seamless workings of the neurons responsible for memory and movement, and researchers around the world have devoted themselves to devising ways of blocking their production or accumulation in humans.. But now a pair of recent research studies from the Stanford University School of Medicine sets a solid course toward rehabilitating the reputation of the proteins that form these amyloid tangles, or plaques. In the process, they appear poised to turn the field of neurobiology on its head.. The first study, published in August, showed that an amyloid-forming protein called beta amyloid, which is strongly implicated in Alzheimers disease, could reverse the symptoms of a multiple-sclerosis-like neurodegenerative disease in laboratory mice.. The second study, published April 3 in Science ...
Background. Renal amyloidosis results from protein misfolding and leads to progressive renal insufficiency. Few data are available concerning the relevance of the histomorphological patterns and the dynamics of the disease process.. Methods. Cases of renal amyloidosis in native kidney biopsies (n = 203) were retrospectively evaluated for the pattern of amyloid distribution, the extent of glomerular amyloid deposition and the amount of interstitial fibrosis and tubular atrophy. One hundred and fifty-eight cases were characterized by immunohistochemistry to determine the biochemical amyloid type. Morphological findings were correlated with available clinical data.. Results. According to the predominant site of amyloid deposition, 84.6% showed a glomerular, 9.4% a vascular and 6% a tubulointerstitial distribution pattern. Within the glomeruli, amyloid was initially deposited in a focal segmental fashion that became diffuse and global in later stages. Most cases were identified as AL lambda (84/158) ...
Carolina Sánchez-López†, Rodrigo Cortés-Mejía‡, Marco C. Miotto§, Andres Binolfi§, Claudio O. Fernández§, Jorge M. del Campo‡, Liliana Quintanar†*. †Departamento de Química, Centro de Investigación y de Estudios Avanzados (Cinvestav), Mexico City, Mexico, ‡Departamento de Física y Química Teórica, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico, §Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario, Argentina.. Abstract. Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits found in pancreatic β-cells of patients with type 2 diabetes (T2D). Copper ions have an inhibitory effect in the amyloid aggregation of hIAPP and they may play a role in the etiology of T2D. ...
Amyloid fibril formation propensity is inherent into the hexapeptide tandemly repeating sequence of the central domain of silkmoth chorion proteins of the A-family Journal Article ...
Self-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimers disease (AD). However, it is clear that not all forms of Aβ are equally harmful and that linking a specific aggregate to toxicity also depends on the assays and model systems used (Haass et al., J Biol. Chem 269:17741-17748, 1994; Borchelt et al., Neuron 17:1005-1013, 1996). Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration. In this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and ΔE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1-based somatic brain transgenesis in mice to selectively
Mercury (Hg) is a bioaccumulating trace metal that globally circulates the atmosphere and waters in its elemental, inorganic and organic chemical forms. While Hg represents a notorious neurotoxicant, the underlying cellular pathways are insufficiently understood. We identify amyloid protein aggregation in the cell nucleus as a novel pathway of Hg-bio-interactions. By mass spectrometry of purified protein aggregates, a subset of spliceosomal components and nucleoskeletal protein lamin B1 were detected as constituent parts of an Hg-induced nuclear aggregome network. The aggregome network was located by confocal imaging of amyloid-specific antibodies and dyes to amyloid cores within splicing-speckles that additionally recruit components of the ubiquitin-proteasome system. Hg significantly enhances global proteasomal activity in the nucleus, suggesting that formation of amyloid speckles plays a role in maintenance of protein homeostasis. RNAi knock down showed that lamin B1 for its part regulates amyloid
Amyloid accumulation is associated with pathological conditions, including type II diabetes and Alzheimers disease. Lipids influence amyloidogenesis and are themselves targets for amyloid-mediated cell membrane disruption. Amyloid precursors are surface-active, accumulating at hydrophobic-hydrophilic interfaces (e.g., air-water), where their biophysical and kinetic behaviors differ from those in the bulk solution with significant and underappreciated consequences. Biophysical modeling predicted the probability and rate of beta-sheet amyloid dimer formation to be higher and faster at the air-water interface (AWI) than in the bulk (by 14 and approximately 1500 times, respectively). Time-course staining experiments with a typical amyloid dye verified our predictions by demonstrating that without AWI, islet amyloid polypeptide (IAPP) fibrilization was abolished or slowed, depending on the conditions. Our controls included undisturbed IAPP reactions, and we ascertained that the AWI removal process
During the study of inhibition of amyloid fibril formation, a-chymotrypsin protein was developed in 55% ethanol at pH 7.0. We investigated the inhibitory effect of different spices on amyloid fibril...
The second WW domain (WW2) of CA150, a human transcriptional activator, forms amyloid fibrils in vitro under physiological conditions. Based on experimental constraints from MAS NMR spectroscopy experiments, alanine scanning and electron microscopy, a structural model of CA150.WW2 amyloid fibrils was calculated earlier. Here, the assignment strategy is presented and suggested as a general approach for proteins that show intermediate line width. The 13C,13C correlation experiments were recorded on fully or partially 13C-labelled fibrils. The earlier 13C assignment (26 residues) was extended to 34 of the 40 residues by direct 13C-excitation experiments by using a deuterated sample that showed strongly improved line width. A 3D HNC-TEDOR (transferred-echo double-resonance) experiment with deuterated CA150.WW2 fibrils yielded 14 amide nitrogen and proton resonance assignments. The obtained chemical shifts were compared with the chemical shifts determined with the natively folded WW domain. TALOS ...
TY - JOUR. T1 - Neurotoxic and gliotrophic activity of a synthetic peptide homologous to Gerstmann-Sträussler-Scheinker disease amyloid protein. AU - Fioriti, Luana. AU - Angeretti, Nadia. AU - Colombo, Laura. AU - De Luigi, Ada. AU - Colombo, Alessio. AU - Manzoni, Claudia. AU - Morbin, Michela. AU - Tagliavini, Fabrizio. AU - Salmona, Mario. AU - Chiesa, Roberto. AU - Forloni, Gianluigi. PY - 2007/2/14. Y1 - 2007/2/14. N2 - Amyloid fibrils in Gerstmann-Sträussler-Scheinker (GSS) disease are composed of a fragment of the prion protein (PrP), the N and C termini of which correspond to ragged residues 81-90 and 144-153. A synthetic peptide spanning the sequence 82-146 (PrP 82-146) polymerizes into protease-resistant fibrils with the tinctorial properties of amyloid. We investigated the biological activity of PrP 82-146 and of two nonamyloidogenic variants of PrP 82-146 with scrambled amino acid sequence 106-126 or 127-146. Cortical neurons prepared from rat and mouse embryos were chronically ...
11C-PIB is believed to bind with conformational dependence to amyloid fibrils of any type-a belief that is in agreement with the results of the present study. The in vitro tissue analysis that was performed in the present study confirmed that there was specific binding of 11C-PIB in heart tissue with amyloid deposits. Amyloid deposits in the myocardium of patients diagnosed with systemic amyloidosis of AL κ, AL λ, and transthyretin origin could be visualized with 11C-PIB, and patients could be identified by visual and semiquantitative assessment of 11C-PIB RI images. In patients with amyloidosis, a significant increase in the 11C-PIB RI was found, whereas MBF was significantly reduced. Obviously, increased 11C-PIB retention was not due to increased MBF. In most patients, 11C-PIB uptake in the myocardium was rather homogeneous, as was MBF. In a single patient (patient 5 in Fig. 2), however, increased 11C-PIB RI was mainly confined to the septum, which showed a corresponding perfusion defect. ...
A novel computational approach to the structural analysis of ordered β-aggregation is presented and validated on three known amyloidogenic polypeptides. The strategy is based on the decomposition of the sequence into overlapping stretches and equilibrium implicit solvent molecular dynamics (MD) simulations of an oligomeric system for each stretch. The structural stability of the in-register parallel aggregates sampled in the implicit solvent runs is further evaluated using explicit water simulations for a subset of the stretches. The beta-aggregation propensity along the sequence of the Alzheimers amyloid-β peptide (Aβ42) is found to be highly heterogeneous with a maximum in the segment V12HHQKLVFFAE22 and minima at S8G9, G25S26, G29A30, and G38V39, which are turn-like segments. The simulation results suggest that these sites may play a crucial role in determining the aggregation tendency and the fibrillar structure of Aβ42. Similar findings are obtained for the human amylin, a 37-residue ...
Box 93, Addenbrookes Hospital, Cambridge CB2 2QQ, UK. MedicalResearch.com: What is the background for your study?. Dr. Menon: We have known for some time that a history of traumatic brain injury (TBI) results in a significant (between 2 and 10 fold) increase in the likelihood of getting dementia in later life. On possible mechanistic explanation for this comes from the finding that about a third of individuals who died of TBI, regardless of age, are found at autopsy to have deposits of β-amyloid in the brain, often Aβ42, which is the same variant of amyloid seen in the brain of patients who have Alzheimers Disease.. However, such detection after death has made it impossible to examine the linkage of such early amyloid deposition to late dementia. More recently, imaging with positron emission tomography (PET) and Pittsburgh compound B (PIB) has been used to image amyloid deposits in Alzheimers Disease. However, the technique had not been validated in traumatic brain ...
The aggregation of human amylin to form amyloid contributes to islet β-cell dysfunction in type 2 diabetes. Studies of amyloid formation have been hindered by the low structural resolution or relatively modest time resolution of standard methods. Two-dimensional infrared (2DIR) spectroscopy, with its sensitivity to protein secondary structures and its intrinsic fast time resolution, is capable of capturing structural changes during the aggregation process. Moreover, isotope labeling enables the measurement of residue-specific information. The diagonal line widths of 2DIR spectra contain information about dynamics and structural heterogeneity of the system. We illustrate the power of a combined atomistic molecular dynamics simulation and theoretical and experimental 2DIR approach by analyzing the variation in diagonal line widths of individual amide I modes in a series of labeled samples of amylin amyloid fibrils. The theoretical and experimental 2DIR line widths suggest a W pattern, as a ...
TY - JOUR. T1 - Methylene blue inhibits amyloid Aβ oligomerization by promoting fibrillization. AU - Necula, Mihaela. AU - Breydo, Leonid. AU - Milton, Saskia. AU - Kayed, Rakez. AU - Van Der Veer, Wytze E.. AU - Tone, Paul. AU - Glabe, Charles G.. PY - 2007/7/31. Y1 - 2007/7/31. N2 - Amyloid plaques are hallmark neuropathological lesions in Alzheimers disease, which consist of abnormally aggregated Aβ protein. Multiple Aβ aggregated species have been identified, and neurotoxicity appears to be correlated with the amount of nonfibrillar oligomers. Therefore, selective inhibition of Aβ oligomer formation has emerged as an attractive means of therapeutic intervention. To investigate whether small molecules can modulate aggregation to achieve selective inhibition of neurotoxic amyloid oligomers, Aβ aggregation was assayed in vitro in the presence of methylene blue, using immunoreactivity with the prefibrillar oligomer-specific antibody A11, transmission electron microscopy, and turbidity ...
In this study, we characterized the biochemical properties of a set of chimeric prion proteins wherein the ORD of Sup35p was replaced with that of PrP. The chimeric prion proteins were created by substituting the endogenous Sup35p ORD with the repeat domain of PrP containing five, eight, 11 and 14 oligopeptide repeats [40]. The repeat-expanded proteins show a remarkable set of properties that highlight their enhanced ability to aggregate and form amyloid fibers in vitro. These data agree with work done by others in which recombinant PrP (rPrP) with ORD expansions exhibit an enhanced ability to form amyloid fibers with increasing number of repeats [20, 46]. Our data also support previous work done with transgenic mice (Tg(PG14)) that express PrP harboring nine additional octapeptide repeats. These mice manifest a spontaneous form of prion disease [21]. Although the spontaneous form of the disease in the Tg(PG14) mice is not infectious, the protein aggregates and the animals display many of the ...
Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels. Transmission electron microscopy (TEM) confirmed amyloid fibrils around perimysial vessels associated with collagen fibrils. A stepwise approach to diagnosis and staging of this disorder is critical and
Looking for online definition of amyloid degeneration in the Medical Dictionary? amyloid degeneration explanation free. What is amyloid degeneration? Meaning of amyloid degeneration medical term. What does amyloid degeneration mean?
TY - JOUR. T1 - Degradation of fibrillar forms of Alzheimers amyloid β-peptide by macrophages. AU - Majumdar, Amitabha. AU - Chung, Haeyong. AU - Dolios, Georgia. AU - Wang, Rong. AU - Asamoah, Nikiya. AU - Lobel, Peter. AU - Maxfield, Frederick R.. PY - 2008/5. Y1 - 2008/5. N2 - Cultured microglia internalize fibrillar amyloid Aβ (fAβ) and deliver it to lysosomes. Degradation of fAβ by microglia is incomplete, but macrophages degrade fAβ efficiently. When mannose-6 phosphorylated lysosomal enzymes were added to the culture medium of microglia, degradation of fAβ was increased, and the increased degradation was inhibited by excess mannose-6-phosphate, which competes for binding and endocytic uptake. This suggests that low activity of one or more lysosomal enzymes in the microglia was responsible for the poor degradation of fAβ. To further characterize the degradation of fAβ in late endosomes and lysosomes, we analyzed fAβ-derived intracellular degradation products in macrophages and ...
Iranian Journal of Diabetes and Metabolism is a quarterly published since 2001 in Persian together with English abstracts. The main scope of this journal is to publish original basic and clinical studies in the special field of diabetes and metabolism. The members of the editorial board of IJDLD are specialists in the fields of endocrinology and biochemistry selected on the basis of their research background from different parts of the country as well as some international authorities in the relevant fields.
Bruno Voigt, Zhanna Evgrafova, Monika Baumann, Madlen Stephani, Marvin Umlandt, Wolfgang H. Binder, Jochen Balbach. Faculty of Natural Sciences II, Martin-Luther-Universität Halle-Wittenberg, D-06120 Halle, Germany. The parathyroid hormone (PTH) is an 84 residue peptide from the parathyroid glands which controls the calcium and phosphate level in human blood. The peptide adopts an α-helical conformation at the N-terminus and is intrinsically disordered at the C-terminus. Amyloidogenic properties of PTH have been reported [1]. Here we show the in vitro formation of amyloid fibrils of PTH 1-84 and of the pharmaceutically relevant N-terminal fragment PTH 1-34 under physiological conditions. To get further insights into the mechanism of amyloid fibrillation we investigated the effect of thermoresponsive polymers [2] on PTH. We covalently attached polyacrylate based polymers to 15N isotope labelled PTH 1-84 and used two dimensional NMR techniques for the characterization of the resulting chimaeras. ...
... , also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis ... Familial amyloid polyneuropathy. From Wikipedia, the free encyclopedia. (Redirected from Transthyretin-related hereditary ... Adams, D; Cauquil, C; Labeyrie, C (October 2017). "Familial amyloid polyneuropathy". Current Opinion in Neurology. 30 (5): 481- ... Scott LJ (August 2014). "Tafamidis: a review of its use in familial amyloid polyneuropathy". Drugs. 74 (12): 1371-8. doi: ...
Beta-amyloid[edit]. Studies in an animal model suggest that oleocanthal can reduce the accumulation of β-amyloid proteins via ... "Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer's ...
β-amyloid is a key neuropathological hallmark of AD, so markers of β-amyloid plaque accumulation in the brain are useful in ... β-amyloid plaques in the brain. It is indicated for Positron Emission Tomography (PET) imaging of β-amyloid neuritic plaque ... Alzheimer's disease and amyloid-beta PET imaging[edit]. More than 44 million people worldwide have been diagnosed with some ... 2011). "Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias". Journal of Nuclear Medicine. 52 (8): ...
... a kidney disorder due to a mutation in the AA amyloid protein gene, has been seen in Abyssinians.[11] The Abyssinian has had ...
... ing is a bacteriological laboratory technique[4] used to differentiate bacterial species into two large groups (gram-positive and gram-negative) based on the physical properties of their cell walls.[5][page needed] Gram staining is not used to classify archaea, formerly archaeabacteria, since these microorganisms yield widely varying responses that do not follow their phylogenetic groups.[6] The Gram stain is not an infallible tool for diagnosis, identification, or phylogeny, and it is of extremely limited use in environmental microbiology. It is used mainly to make a preliminary morphologic identification or to establish that there are significant numbers of bacteria in a clinical specimen. It cannot identify bacteria to the species level, and for most medical conditions, it should not be used as the sole method of bacterial identification. In clinical microbiology laboratories, it is used in combination with other traditional and molecular techniques to identify bacteria. Some ...
The genus Mycobacterium is a slow growing bacteria, made up of small rods that are slightly curved or straight, and are considered to be gram positive. Some types of Mycobacteria form branches or filaments. Some mycobacteria are free-living saprophytes, but many are pathogens that cause disease in animals and humans. Mycobacterium bovis causes tuberculosis in cattle. Since tuberculosis can be spread to humans, milk is pasteurized to kill any of the bacteria.[1]Some Mycobacteria species that cause disease in humans include Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium bovis, Mycobacterium africanum and members of the Mycobacterium avium complex. Mycobacterium tuberculosis is a species of Mycobacterium that causes tuberculosis (TB). Mycobacterium tuberculosis is an airborne bacterium that typically infects the human lungs.[2][3] Symptoms of TB include a bad cough, chest pain, fatigue, weight loss, no appetite, chills, fever and night sweats.[4] The typical ...
The preparatory steps involved depend on the type of analysis planned; some or all of the following procedures may be required.. Fixation-which may itself consist of several steps-aims to preserve the shape of the cells or tissue involved as much as possible. Sometimes heat fixation is used to kill, adhere, and alter the specimen so it accepts stains. Most chemical fixatives (chemicals causing fixation) generate chemical bonds between proteins and other substances within the sample, increasing their rigidity. Common fixatives include formaldehyde, ethanol, methanol, and/or picric acid. Pieces of tissue may be embedded in paraffin wax to increase their mechanical strength and stability and to make them easier to cut into thin slices.. Permeabilization involves treatment of cells with (usually) a mild surfactant. This treatment dissolves cell membranes, and allows larger dye molecules into the cell's interior.. Mounting usually involves attaching the samples to a glass microscope slide for ...
Amyloid beta is produced in the brain by enzymes that divide a larger protein - the amyloid precursor protein (APP) - into ... AMYLOID BETA[redigér , redigér wikikode]. One of the most common areas of research in the fight against Alzheimer's disease ... focuses on amyloid beta, the sticky proteins that clump together in the brain, forming plaques that choke nerve cells and ... resulting in the production of amyloid beta [[4]] [[5]] ...
Amyloid plaque. *Atheroma or atheromatous plaque, a buildup of deposits within the wall of an artery ...
... called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor ... beta amyloid: the major component of senile plaques in Alzheimer's disease.. *prion: main component of prion diseases and ... Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of ... Ohnishi S, Takano K (March 2004). "Amyloid fibrils from the viewpoint of protein folding". Cell. Mol. Life Sci. 61 (5): 511-24 ...
Amyloid imaging in aging and dementia: Testing the amyloid hypothesis in vivo. „Behav Neurol". 21 (1), s. 117-28, 2009. DOI: ... a b Ohnishi S, Takano K. Amyloid fibrils from the viewpoint of protein folding. „Cell. Mol. Life Sci.". 61 (5), s. 511-24, 03 ... amyloid precursor protein, prekursorowe białko amyloidu) na chromosomie 21. Informacja ta wiąże się z prawie pewnym ... Homeostatyczna naprawa mieliny przyczynia się do rozwoju depozytów białkowych, takich jak beta-amyloid czy tau[52][53][54]. ...
Amyloid hypothesis. In 1991, the amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the ... Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the ... September 2015). "Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy". Nature. 525 (7568): ... called amyloid beta (Aβ). Aβ is a fragment from the larger amyloid precursor protein (APP). APP is a transmembrane protein that ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
In addition, thiamine deficiency and oxidative stress can be linked to the formation of the beta-amyloid(Aβ) plaques, and this ... In general, Aβ peptide is produced by the cleavage of the parental amyloid precursor protein (APP) that is located at plasma ... Figure 1: The resulted neuritic plaques of beta-amyloid (Aβ) peptide and neurofibrillary tangles of tau protein in brain ... The hallmarks of AD are neuritic plaques of beta-amyloid (Aβ) peptide and neurofibrillary tangles (NFTs) of tau protein in ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
Drugs to block this enzyme (BACE inhibitors) in theory would prevent the buildup of beta-amyloid and (per the Amyloid ... Beta-secretase 1 (BACE1), also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 ... amyloid-beta binding. • beta-aspartyl-peptidase activity. • GO:0001948 protein binding. • enzyme binding. • hydrolase activity ... amyloid-beta metabolic process. • membrane protein ectodomain proteolysis. • modulation of chemical synaptic transmission. • ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
1991年,學者提出類澱粉胜肽假說,認為β類澱粉胜肽(英语:Beta amyloid)(Aβ)在大腦堆積可能是導致阿茲海默症的根本原因[79][80]。根據研究發現表現Aβ的前類澱粉蛋白質基因(APP)位在第21對染色體
Amyloid light-chain (AL) amyloidosis, also known as primary amyloidosis, is the most common form of systemic amyloidosis in the ... These light chains come together to form amyloid deposits which can cause serious damage to different organs.[2][3] Abnormal ... "BU: Amyloid Treatment & Research Program". Archived from the original on 2008-07-20.. ... Both blood and the urine can be tested for the light chains, which may form amyloid deposits, causing disease. However, the ...
Beta-amyloid production[edit]. Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) ... amyloid-beta formation. • amyloid precursor protein metabolic process. • neutrophil degranulation. • regulation of canonical ... A 5-fold drop of amyloid peptide was observed, suggesting that deficiency of presenilin-1 can down regulate amyloid and ... from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.[6] ...
Amyloid deposits deriving from islet amyloid polypeptide (IAPP, or amylin) are commonly found in pancreatic islets of patients ... It is thought that proIAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid ... Paulsson JF, Westermark GT (July 2005). "Aberrant processing of human proislet amyloid polypeptide results in increased amyloid ... "Entrez Gene: IAPP islet amyloid polypeptide".. *^ a b c Higham CE, Hull RL, Lawrie L, Shennan KI, Morris JF, Birch NP, Docherty ...
beta-amyloid binding. · acetylcholinesterase activity. · acetylcholinesterase activity. · carboxylesterase activity. · ... amyloid precursor protein metabolic process. · neurotransmitter receptor biosynthetic process. · regulation of dendrite ... Pakaski M, Kasa P. Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein.. Current drug ...
Amylin, also known as islet amyloid polypeptide (IAPP).[17] The function of amylin is to slow the rate of glucose entering the ...
Beta-amyloid is a small piece of a larger protein called the amyloid precursor protein (APP). Once APP is activated it is cut ... Deposits of amyloid can be seen in sections of brain tissue. This amyloid protein forms plaques and neurofibrillary tangles ... One of the fragments produced in this cutting process is β-amyloid. β-amyloid is "stickier" than any other fragment produced ... "Increased β-amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the ...
However, a similar amount of amyloid plaque was found.[18] More recent research has extended established findings of age ...
"The ER stress factor XBP1s prevents amyloid-beta neurotoxicity". Human Molecular Genetics. 20 (11): 2144-60. doi:10.1093/hmg/ ...
... is thus a potential therapeutic under the amyloid hypothesis.[4] According to the Dorlands Medical Dictionary, it ... it is reported to be an inhibitor of amyloid beta protein (Aβ) fiber formation, whose presence is a hallmark of Alzheimer's ... "New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's ...
"Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect". Frontiers in Physiology. 5: 522. doi:10.3389/ ...
Explore an interactive diagram of beta-amyloid formation and how they contribute to the development of plaques in the ... Beta-amyloid is chemically "sticky" and gradually builds up into plaques.. The most damaging form of beta-amyloid may be groups ... Plaques form when protein pieces called beta-amyloid (BAY-tuh AM-uh-loyd) clump together. Beta-amyloid comes from a larger ...
2011) Amyloid. In: Khan M.G. (eds) Encyclopedia of Heart Diseases. Humana Press. * .RIS Papers ... Gertz MA, Skinner M, Connors LH et al (1985) Selective binding of nifedipine to amyloid fibrils. Am J Cardiol 55:1646PubMed ... Rubinow A, Skinner M, Cohen AS (1981) Digoxin sensitivity in amyloid cardiomyopathy. Circulation 63:1285-1288PubMedGoogle ... Pepys MB, Herbert J, Hutchinson WL et al (2002) Targeted pharmacological depletion of serum amyloid P component for treatment ...
Familial amyloid polyneuropathy, also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis ... Familial amyloid polyneuropathy. From Wikipedia, the free encyclopedia. (Redirected from Transthyretin-related hereditary ... Adams, D; Cauquil, C; Labeyrie, C (October 2017). "Familial amyloid polyneuropathy". Current Opinion in Neurology. 30 (5): 481- ... Scott LJ (August 2014). "Tafamidis: a review of its use in familial amyloid polyneuropathy". Drugs. 74 (12): 1371-8. doi: ...
Cutting-edge and authoritative, Amyloid Proteins: Methods and Protocols, Third Edition is a valuable resource for both students ... Mapping Amyloid Regions in Gad m 1 with Peptide Arrays Rosa Sánchez, Javier Martínez, Laura Montoya, Milagros Castellanos, ... The chapters in this book are divided into three parts: Part One covers in vitro assays that focus on a variety of amyloids and ... Part Two describes cell culture models and assays, and Part Three explores methods on how to extract amyloid from tissue, its ...
Glenner thought that amyloid-β might be the cause of Alzheimers disease, but the amyloid hypothesis did not take off until the ... The fact that such plaques consist of amyloid-β, combined with the discovery of mutations that increase amyloid-β aggregation, ... Even the staunchest supporters of the amyloid hypothesis think that amyloid-β is not the only target worthy of intervention, ... the amyloid hypothesis, which is the assumption that accumulation of the peptide amyloid-β is the main cause of the condition. ...
Imagine if doctors could determine, many years in advance, who is likely to develop dementia. Such prognostic capabilities would give patients and their families time to plan and manage treatment.... ...
encoded search term (What is amyloid arthropathy?) and What is amyloid arthropathy? What to Read Next on Medscape. Related ... A primer of amyloid nomenclature. Amyloid. 2007 Sep. 14(3):179-83. [Medline]. ... had amyloid deposition. At 10-year follow-up, only 2 patients had systemic amyloidosis diagnosed after amyloid was discovered ... What is amyloid arthropathy?. Updated: May 09, 2019 * Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD more ...
Treatment of amyloid neuropathies is directed at both preventing further deposition of amyloid in peripheral nerves and ... Amyloid Neuropathy. Disorders of peripheral nerves are the most common neurological complications of systemic amyloidosis; an ... Diagnosis of amyloid neuropathies is based on history, clinical examination and supporting laboratory investigations. These ... Depending on the type of amyloid protein, patients may benefit from liver or bone marrow transplant. Neuropathic pain due to ...
... prolactin or prolactin fragments are found in the pituitary amyloid. This condition is often observed in elderly people and has ... encoded search term (What is prolactin amyloid (Apro)?) and What is prolactin amyloid (Apro)? What to Read Next on Medscape. ... In prolactin amyloid (Apro), prolactin or prolactin fragments are found in the pituitary amyloid. This condition is often ... A primer of amyloid nomenclature. Amyloid. 2007 Sep. 14(3):179-83. [Medline]. ...
The amyloid cascade hypothesis postulates that the initial event which triggers neuronal degradation in Alzheimers disease is ... What is amyloid?. The function of amyloid is not yet fully understood; however, it has been shown to contribute to several ... The amyloid plaques previously described are the products of amyloid-β (Aβ) accumulation. These Aβ fragments are generated from ... What is the amyloid cascade hypothesis?. The amyloid cascade hypothesis was initially suggested in 1992. This theory postulates ...
Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), ... Genetic Testing Registry: Cerebral amyloid angiopathy, APP-related *Genetic Testing Registry: Hereditary cerebral amyloid ... Hereditary cerebral amyloid angiopathy caused by mutations in the APP, CST3, or ITM2B gene is inherited in an autosomal ... Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. APP gene mutations cause the ...
Amyloid, Prions, and Other Protein Aggregates. Volume 309, Part 1 of Amyloid, Prions, and Other Protein Aggregates: Part [A]-C ...
Is it time to rethink the notion that amyloid deposits in the brain drive this disease? ... The hope was that if the drug could eliminate soluble amyloid-beta-the protein blamed for the brain plaques that form in ... The hope was that if the drug could eliminate soluble amyloid-beta-the protein blamed for the brain plaques that form in ... "While the results of Expedition3 were not what we had hoped they would be, we believe the amyloid hypothesis should continue to ...
2000) Amyloid formation in the rat: Adenoviral expression of mouse serum amyloid A proteins. Amyloid 7(1):32-40. ... 1997) Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nat Med 3(8):855-859. ... Deposition of AA amyloid in humans may thus also be triggered by such an amyloid fibril seed, but it has not hitherto been ... Significant minor amyloid deposits were also present in the kidneys, heart, and gut (Fig. S2). The total amyloid load was much ...
Treatment with a new compound that precisely targets and blocks only amyloid precursor protein reduced plaque accumulation by ... The researchers explain that other experimental drugs that tackle amyloid proteins target the enzymes that cleave beta-amyloid ... "Alzheimers amyloid protein development halted in mice." Medical News Today. MediLexicon, Intl., 30 Apr. 2015. Web.. 23 Jan. ... 2-week treatment led to 50% reduction in amyloid plaques in mice. Prof. Dewji - who is also president and CEO of Cenna, the ...
Amyloid proteins, for example, can self-assemble into the tangled plaques associated with Alzheimers disease -- but can also ... Davis and Rice University have now come up with methods to manipulate natural proteins so that they self-assemble into amyloid ... Engineering self-assembling amyloid fibers. University of California - Davis. Journal. ACS Nano. Funder. UC Davis RISE. ... engineering-self-assembling-amyloid-protein-surfaces/. More in Chemistry & Physics. * Chocolate muddles cannabis potency ...
... a drug that clears amyloid plaque from the brain, halting the disease. ... The drugmakers themselves have said that in 81 percent of the group taking the highest dose of BAN2401, the amount of amyloid ... showed how the drug not only cleared out significant amounts of amyloid plaque (a hallmark of the disease) but also seemed to ...
Temperature dependence of amyloid β-protein fibrillization. Yoko Kusumoto, Aleksey Lomakin, David B. Teplow, George B. Benedek ... Temperature dependence of amyloid β-protein fibrillization. Yoko Kusumoto, Aleksey Lomakin, David B. Teplow, George B. Benedek ... Temperature dependence of amyloid β-protein fibrillization. Yoko Kusumoto, Aleksey Lomakin, David B. Teplow, and George B. ... Fibrillogenesis of the amyloid β-protein (Aβ) is believed to play a central role in the pathogenesis of Alzheimers disease. ...
This entry represents the propeptide (Pro-islet amyloid polypeptide) prior to cleavage into islet amyloid polypeptide. ... Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide or amylin) is a pancreatic islet hormone that is ... stored with insulin in beta cell granules [PMID: 2192709]. IAPP has a propensity to form islet cell-disrupting amyloid deposits ...
Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by ... Two of the main isoforms, amyloid-beta40 (Abeta40) and amyloid-beta42 (Abeta42), are found prominently in the extracellular ... Amyloid beta A4 protein (also known as APP or A4) consists of a large N-terminal extracellular region containing heparin- ... The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.. Biochem. Biophys. Res. Commun. 341 1-5 2006 ...
Mechanism for Amyloid-beta Accumulation in Alzheimers Disease Mechanism for Amyloid-beta Accumulation in Alzheimers Disease ... which normally removes amyloid-beta from the brain. The copper accumulation was also linked with higher brain amyloid-beta ... Low levels of copper disrupt brain amyloid-beta homeostasis by altering its production and clearance. Proc Natl Acad Sci U S A ... An NIEHS grantee and colleagues report that low levels of copper can accumulate in the brain, leading to amyloid-beta plaques ...
The effect of the buildup of beta amyloid in the brain, caused by a variation of a gene known as CYP46, is memory loss better ... The effect of the buildup of beta amyloid in the brain, caused by a variation of a gene known as CYP46, is memory loss better ... People who suffer from Alzheimers more often have high levels of beta amyloid which collect in clumps, called senile plaques ... Most researchers now agree that beta amyloid buildup is most certainly involved in the disruption of memory and thought. ...
Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated ... Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, ... Amyloid goiter is clinically defined as the deposition of amyloid in the thyroid gland in such quantities as to produce an ... To date, an approximate total of 85 cases of amyloid goiter have been reported in the literature. Deposition of amyloid in the ...
the epitope lies within amino acids 18-22 of beta amyloid (VFFAE) ... β-Amyloid (4G8). Quick Links. *Overview. *Comments / Questions ...
immunogen = soluble Amyloid oligomers. Specificity. generic epitope common to prefibrillar oligomers and not fibrils, monomers ... Apolipoprotein A-I deficiency increases cerebral amyloid angiopathy and cognitive deficits in APP/PS1DeltaE9 mice. J Biol Chem ...
All posts tagged with amyloid beta. * Preventing Alzheimers: Scientists develop blood test capable of detecting toxic protein ...
Bacterial Inclusion Bodies Contain Amyloid-Like Structure at SciVee Amyloid Cascade Hypothesis Amyloid: Journal of Protein ... November 2000). "Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimers beta-amyloid peptide, ... The "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built ... Functional amyloid in Homo sapiens: Intralumenal domain of melanocyte protein PMEL Peptide/protein hormones stored as amyloids ...
Make research projects and school reports about amyloid easy with credible articles from our FREE, online encyclopedia and ... amyloid (am-i-loid) n. a glycoprotein, resembling starch, that is deposited in the internal organs in amyloidosis. β-amyloid ... amyloid A Dictionary of Plant Sciences © A Dictionary of Plant Sciences 1998, originally published by Oxford University Press ... amyloid A Dictionary of Biology © A Dictionary of Biology 2004, originally published by Oxford University Press 2004. ...
Finally, the role of amyloid formation in bacteria will be reviewed. The recent finding that bacteria can make amyloid in a ... However, it is becoming increasingly clear that amyloid is also present in the healthy setting; for example nontoxic amyloid ... Amyloid formation: functional friend or fearful foe?. Bergman P1, Roan NR2,3, Römling U4, Bevins CL5, Münch J6,7. ... The role of amyloid in health and disease is beginning to be unravelled, and here, we will review some of the most recent ...
Islet amyloid polypeptide (IAPP; amylin), the major component of islet amyloid, is co-secreted with insulin from beta-cells. In ... have been proposed to contribute to the development of islet amyloid deposits. Inhibitors of islet amyloid fibril formation ... Islet amyloid polypeptide and type 2 diabetes.. Marzban L1, Park K, Verchere CB. ... The mechanism(s) responsible for islet amyloid formation in type 2 diabetes is still unclear but it appears that an increase in ...
  • Their development was guided by an idea that has dominated research on Alzheimer's disease for more than 25 years: the amyloid hypothesis, which is the assumption that accumulation of the peptide amyloid-β is the main cause of the condition. (nature.com)
  • Amyloid-β is therefore an obvious therapeutic target - if you can deal with the peptide, then you can treat the condition. (nature.com)
  • Some success in preclinical studies evolved into this idea that what we need to do is remove the soluble form of the [amyloid-beta] peptide from the brain. (forbes.com)
  • Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide or amylin) is a pancreatic islet hormone that is stored with insulin in beta cell granules [ PMID: 2192709 ]. (ebi.ac.uk)
  • By this definition, fewer than 25 amyloid-forming proteins have been identified and associated with serious diseases, including amyloid- β peptide (A β ) with Alzheimer's disease (AD), islet amyloid polypeptide (IAPP) with diabetes type 2, and prion protein (PrP) with the spongiform encephalopathies [ 3 ]. (hindawi.com)
  • Functional amyloid in Homo sapiens: Intralumenal domain of melanocyte protein PMEL Peptide/protein hormones stored as amyloids within endocrine secretory granules Receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3) Fragments of prostatic acid phosphatase and semenogelins Functional amyloid in other organisms: Curli fibrils produced by E. coli, Salmonella, and a few other members of the Enterobacteriales (Csg). (wikipedia.org)
  • First, the amyloid-forming properties of the antimicrobial peptide human defensin 6 (HD6) will be considered. (nih.gov)
  • In type 2 diabetes, this peptide aggregates to form amyloid fibrils that are toxic to beta-cells. (nih.gov)
  • If there was pre-symptomatic evidence that amyloid levels were too high in a patient's brain, a GSM might be taken to lower relevant peptide levels and reduce AD risk. (eurekalert.org)
  • In this study, we aimed to identify the effects of amyloid-β peptide 42 (amyloid-β42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. (gu.se)
  • We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-β peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. (gu.se)
  • In earlier work, Eisenberg's colleague Melinda Balbirnie discovered that a short segment of an amyloid protein - a peptide only seven amino acids long - could form a steric zipper. (emaxhealth.com)
  • It wasn't until 1987 that the amyloid peptide was described as the main component of these deposits, known as amyloid plaques. (esrf.fr)
  • Amyloid peptide is processed in the extracellular space in the brain and tends to aggregate, forming oligomers that further develop into amyloid fibrils in a nucleation-dependent polymerisation process. (esrf.fr)
  • Two different types of amyloid peptide aggregates were found: fibrils (which have been previously described) and - identified for the first time in affected brains - non-fibrillary aggregates with a high component of disordered structure. (esrf.fr)
  • Wild-type, full-length (40- and 42-residue) amyloid β-peptide (Aβ) fibrils have been shown by a variety of magnetic resonance techniques to contain cross-β structures in which the β-sheets have an in-register parallel supramolecular organization. (rcsb.org)
  • A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-β peptide of 40-42 amino acid residues 1 . (nature.com)
  • Many scientists believe that plaques made of amyloid peptide contribute to brain degeneration in people with Alzheimer's disease. (acs.org)
  • Functional amyloids play a beneficial role in a variety of physiologic processes (eg, long-term memory formation, gradual release of stored peptide hormones). (medscape.com)
  • Alpha-helix targeting reduces amyloid-beta peptide toxicity. (uniprot.org)
  • The amyloid-beta peptide (Abeta) can generate cytotoxic oligomers, and their accumulation is thought to underlie the neuropathologic changes found in Alzheimer's disease. (uniprot.org)
  • Immunohistochemical analysis of paraffin-embedded human Alzheimer's brain using β-Amyloid (D12B2) Rabbit mAb in the presence of control peptide (left) or antigen-specific peptide (right). (cellsignal.com)
  • The interventions now propose to study the effects of an SSRI ( escitalopram ) on levels of amyloid beta peptide (the major constituent of the plaques) in the cerebrospinal fluid (CSF) of cognitively normal older adults. (clinicaltrials.gov)
  • The amyloid-beta (A beta) peptide is a cytotoxic peptide implicated in the pathology of Alzheimer's disease (AD). (nih.gov)
  • Gallic acid, or GA, coats the surfaces of amyloid fibrils in semen to prevent HIV infectivity enhancement and coats the peptide precursors to prevent fibril formation. (asbmb.org)
  • We propose a working model of A-body biogenesis that includes a role for low complexity ribosomal intergenic spacer RNA (rIGSRNA) and a discrete peptide sequence, the amyloid-converting motif (ACM), found in many proteins that undergo immobilization. (frontiersin.org)
  • Peptide and protein hormones are stored in secretory granules in a nonpathological amyloid conformation. (sciencemag.org)
  • Accumulations of amyloid β (Aβ) in the brain contribute to the development of Alzheimer's disease, so scientists have long puzzled over why the body produces this peptide. (acs.org)
  • Pepys MB, Herbert J, Hutchinson WL et al (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. (springer.com)
  • Familial amyloid polyneuropathy , also called transthyretin-related hereditary amyloidosis , transthyretin amyloidosis abbreviated also as ATTR (hereditary form), or Corino de Andrade's disease , [1] is an autosomal dominant [2] neurodegenerative disease. (wikipedia.org)
  • Amyloid deposition in inflammatory syndromes is amplified by the underlying inflammatory state, significantly increasing morbidity and mortality, especially in the case of renal amyloidosis. (medscape.com)
  • In a pathology review of 124 patients undergoing carpal tunnel release without a previous diagnosis or clinical signs of amyloidosis, 82% had amyloid deposition. (medscape.com)
  • At 10-year follow-up, only 2 patients had systemic amyloidosis diagnosed after amyloid was discovered in their tenosynovium. (medscape.com)
  • Amyloidosis can affect peripheral sensory, motor or autonomic nerves and deposition of amyloid lead to degeneration and dysfunction in these nerves. (hopkinsmedicine.org)
  • Kishida D, Okuda Y, Onishi M, Takebayashi M, Matoba K, Jouyama K. Successful tocilizumab treatment in a patient with adult-onset Still's disease complicated by chronic active hepatitis B and amyloid A amyloidosis. (medscape.com)
  • In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. (hindawi.com)
  • Amyloidosis is a general term describing a group of diseases characterized by the deposition of an insoluble, proteinaceous, amorphous, and eosinophilic material, called amyloid, in the extracellular matrix of some organs and tissues [ 1 ]. (hindawi.com)
  • Primary amyloidosis is characterized by the deposition of amyloid L (AL), which is the major fibrillary protein originating from the light chain components of immunoglobulins, whereas secondary amyloidosis is characterized by the deposition of amyloid A (AA), which constitutes a portion of the acute-phase serum amyloid A (SAA) protein produced by the liver during inflammation. (hindawi.com)
  • Deposition of amyloid in the thyroid gland may coexist with systemic amyloidosis, with medullary thyroid carcinoma, and less commonly with primary amyloidosis involving the thyroid gland. (hindawi.com)
  • Such amyloids have been associated with (but not necessarily as the cause of) more than 50 human diseases, known as amyloidosis, and may play a role in some neurodegenerative disorders. (wikipedia.org)
  • The International Society of Amyloidosis classifies amyloid fibrils and their associated diseases based upon associated proteins (for example ATTR is the group of diseases and associated fibrils formed by TTR). (wikipedia.org)
  • amyloid Tissue consisting of protein fibrils that may accumulate between cells in various animal tissues, especially in the disorder amyloidosis . (encyclopedia.com)
  • amyloid ( am -i-loid) n. a glycoprotein, resembling starch, that is deposited in the internal organs in amyloidosis. (encyclopedia.com)
  • Amyloid formation has been most studied in the context of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as in amyloidosis. (nih.gov)
  • The Stanford Amyloid Center comprises a comprehensive team of physicians, scientists, nurses, and counselors dedicated to improving the care of patients with amyloidosis. (stanford.edu)
  • Since its founding in 2008, the Stanford Amyloid Center has grown into one of the largest treatment centers for amyloidosis in the world and the largest in the western United States. (stanford.edu)
  • Areas of active clinical research relevant to cardiac amyloidosis include cardiac imaging that uses magnetic resonance imaging (MRI) and nuclear imaging (using the pyrophosphate or PYP scan), studies examining the biochemical basis of amyloid toxicity, and projects examining the best treatment of patients with cardiac amyloidosis. (bmc.org)
  • For further information regarding the program or ongoing research studies, or to refer a patient with amyloidosis, please contact the program office at 617.638.4317 or visit the Amyloid Center Webpage . (bmc.org)
  • Beta-Amyloid (A ) peptides, made up of long, insoluble ordered fibers, are glycoproteins deposited extracellularly in tissues in amyloidosis. (anaspec.com)
  • For instance, in one type of amyloidosis known as AL, chemotherapy is required, but chemo is inappropriate and potentially harmful to patients with other amyloid conditions," Dr Hill said. (edu.au)
  • Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
  • Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
  • Only 10% of amyloidosis deposits consist of components such as glycosaminoglycans (GAGs), apolipoprotein-E (apoE), and serum amyloid P-component (SAP), while nearly 90% of the deposits consist of amyloid fibrils that are formed by the aggregation of misfolded proteins. (medscape.com)
  • The modern era of amyloidosis classification began in the late 1960s with the development of methods to solubilize amyloid fibrils. (medscape.com)
  • In a presumed prion-like mechanism, amyloid fibrils have been shown to trigger and accelerate the development of AA amyloidosis in rodent models. (environmental-expert.com)
  • The finding of amyloid fibrils in edible avian and mammalian food animal tissues, combined with the inability of cooking temperatures to eliminate their amyloidogenic potential, has led to concerns that products such as pate de foie gras may activate a reactive systemic amyloidosis in susceptible consumers. (environmental-expert.com)
  • Writing in the journal PLOS ONE , researchers from the University of California-San Diego (UCSD) School of Medicine and Cenna Biosciences, Inc. describe how they identified compounds that block the production of beta-amyloid peptides in mice. (medicalnewstoday.com)
  • The P8 compound in this new study does not act on enzymes - it binds to APP and blocks the process that cuts it up into the smaller amyloid peptides. (medicalnewstoday.com)
  • High levels of these peptides, particularly A-beta 42, have been linked to the creation of beta-amyloid plaques in Alzheimer's disease, a neurodegenerative condition that afflicts 5.3 Americans and more than 26 million people worldwide. (eurekalert.org)
  • A major pathological feature of Alzheimer's disease is the presence of cerebral senile plaques with aggregated amyloid beta (Aβ) peptides as the main constituent. (kth.se)
  • The test for CSF Beta-Amyloid by LC-MS/MS monitors both CSF beta-amyloid 40 (AB40) and 42 (AB42) endogenous peptides, rather than only AB42. (questdiagnostics.com)
  • The quantitation of both AB peptides permits the normalization of beta amyloid levels circulating in cerebrospinal fluid in different patients by using a ratio of beta-amyloid 42/beta-amyloid 40, resulting in an improved sensitivity for monitoring cognitive impairment that can progress to Alzheimer's disease. (questdiagnostics.com)
  • The causes of Alzheimer's disease (AD) are still unclear, but postmortem examination of patient's brains reveal abundant senile plaques composed of amyloid-beta (Aa) peptides and neurofibrillary tangles formed by filaments of highly phosphorylated tau protein. (sbir.gov)
  • By studying peptides from 10 different amyloid-forming proteins, Eisenberg found three different types of variation in the steric zippers. (emaxhealth.com)
  • Next, he found that some amyloid-forming peptides were flipped relative to each other - much like two hands folding palm to back-of-hand, rather than palm-to-palm. (emaxhealth.com)
  • The technique is particularly useful in the case of amyloid aggregation, since the aggregated peptides/proteins generate very specific and easily identifiable spectroscopic bands in the mid-infrared regions (between 1620 and 1630 cm-1) [2] . (esrf.fr)
  • The role of metal cations is also a highly discussed topic in relation to Alzheimer's disease since metals, together with the amyloid peptides, may be involved in a redox reaction that could lead to oxidative stress, which could be related to the development of the disease. (esrf.fr)
  • Aβ peptides are produced by the proteolytic cleavage of the transmembrane protein amyloid precursor protein (APP) by enzyme complexes a, β and γ-secretases. (news-medical.net)
  • Here we crystallographically characterize designed peptides that assemble into spiraling cross-α amyloid-like structures, which resemble twisted β-amyloid fibrils. (rcsb.org)
  • The peptides form helical dimers, stabilized by packing of small and apolar residues, and the dimers further assemble into cross-α amyloid-like fibrils with superhelical pitches ranging from 170 Å to 200 Å. (rcsb.org)
  • These peptides are generated as cleavage products 39 to 43 amino acids in length from the membrane protein, Amyloid Precursor Protein (APP) by two proteases, -secretase and γ-secretase. (anaspec.com)
  • Heterogeneity at both ends of the peptides is known to affect the toxicity of beta-amyloid peptides. (anaspec.com)
  • Amyloid deposits are insoluble and the core component of these plaques are A peptides that are 39 to 42 amino acid residues in length with a molecular mass of approximately 4 kDa. (anaspec.com)
  • Polymorphisms that slightly vary native peptides or inflammatory processes set the stage for abnormal protein folding and amyloid fibril deposition. (medscape.com)
  • These peptides spontaneously self-assembled in water to form fibril structures (pictured) resembling those that make up the amyloid-β plaques found in the brains of Alzheimer s patients. (phys.org)
  • Western blot analysis of the indicated amounts of human Aβ-42 (left) and Aβ-40 (right) peptides using β-Amyloid (D12B2) Rabbit mAb. (cellsignal.com)
  • Offering a potential early intervention for Alzheimer's disease (AD), researchers at University of California, San Diego School of Medicine and Cenna Biosciences, Inc. have identified compounds that block the production of beta amyloid peptides in mice. (ucsd.edu)
  • The P8 compound does not act on enzymes, but rather binds to APP and in so doing, prevents the larger protein from being processed into smaller amyloid peptides. (ucsd.edu)
  • Together with his colleague Caine Wong, Glenner showed that it is derived from a larger protein called amyloid precursor protein (APP), which sits in and crosses the cell membrane. (nature.com)
  • Alzheimer's disease can be either sporadic or familial, with common mutations found in amyloid precursor protein (APP) and presenilin genes. (news-medical.net)
  • The APP gene provides instructions for making a protein called amyloid precursor protein. (medlineplus.gov)
  • In the brain, the amyloid precursor protein plays a role in the development and maintenance of nerve cells (neurons). (medlineplus.gov)
  • Additionally, the ITM2B protein may be involved in processing the amyloid precursor protein. (medlineplus.gov)
  • She and her colleagues believe it is likely the new drug would have few side effects because of how it acts specifically on one target - amyloid precursor protein (APP). (medicalnewstoday.com)
  • The researchers explain that other experimental drugs that tackle amyloid proteins target the enzymes that cleave beta-amyloid from its larger precursor protein APP. (medicalnewstoday.com)
  • The amyloid precursor protein and postnatal neurogenesis/neuroregeneration. (ebi.ac.uk)
  • Other factors, such as impairment in the processing of proIAPP, the IAPP precursor, have been proposed to contribute to the development of islet amyloid deposits. (nih.gov)
  • This is Merck's oral inhibitor of beta secretase or BACE, one of the enzymes (the other principal one is gamma secretase) that cleaves beta-amyloid protein from a larger precursor molecule. (medpagetoday.com)
  • We therefore created a free online knowledge database (AMYPdb) dedicated to amyloid precursor proteins and we have performed large scale sequence analysis of the included data. (nih.gov)
  • ADAMs family members as amyloid precursor protein α‐secretases. (news-medical.net)
  • 1999). Purification and cloning of amyloid precursor protein β-secretase from human brain. (news-medical.net)
  • Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. (gu.se)
  • APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. (gu.se)
  • It decreases the amount of plaque-forming beta-amyloid protein by changing the point at which gamma secretase cleaves the amyloid precursor protein. (thefreedictionary.com)
  • Additionally, the gallic acid-coated fibrils prevent the formation of new amyloid fibrils by binding the precursor components and changing their charge characteristics. (asbmb.org)
  • Because of the currently perceived role of beta amyloid in disease progression, several investigational drugs have targeted the enzymes that cleave beta amyloid from its larger precursor protein, the aptly named amyloid precursor protein (APP). (ucsd.edu)
  • Professor Kenneth Kosik describes the relationship between the amyloid precursor protein (APP) and Alzheimer's disease. (dnalc.org)
  • As we go deeper in the study of Alzheimer's disease and move down to the level of the gene, we know that the protein in the senile plaque is encoded by a gene called the amyloid precursor protein gene. (dnalc.org)
  • That gene is critically important for the Alzheimer's disease process, not only because it's the product of that gene that forms the plaque but also, in a few rare cases of the disease, mutations in the amyloid precursor gene can lead to early-onset Alzheimer's disease. (dnalc.org)
  • Amyloid precursor protein (APP) is expressed in the synapses of neurons and is thought to be responsible for forming and repairing synapses. (dnalc.org)
  • There are also two ongoing trials of solanezumab that could prove valuable, because they address the question of whether clearing amyloid-beta in healthy people who face a high risk of developing Alzheimer's can actually prevent the most debilitating symptoms. (forbes.com)
  • This seeds the accumulation of amyloid-β into larger structures called oligomers. (nature.com)
  • The amyloid plaques previously described are the products of amyloid-β (Aβ) accumulation. (news-medical.net)
  • Neurodegeneration occurs when changes in APP processing lead to the accumulation of beta-amyloid which goes on to affect surrounding neurons and other tissues, through oxidative damage which affects many other signalling pathways leading ultimately to apoptosis. (bio.net)
  • Two potential sources of chronic stress are the accumulation of clumps of beta-amyloid protein in the brain, a known hallmark of Alzheimer's, and diseased arteries which are also linked to dementia. (thefreedictionary.com)
  • Objective: Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET). (mendeley.com)
  • The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory. (mendeley.com)
  • While none of the patients exhibited signs of dementia before their deaths, most had moderate to severe accumulation of amyloid-β in their brains. (the-scientist.com)
  • But when Collinge and his colleagues looked at the brains of patients who'd died of CJD but had not received cadaver-derived growth hormone treatments, they found no evidence of amyloid-β accumulation in similarly aged individuals. (the-scientist.com)
  • They found that adults ages 50 to 59 who had amyloid were twice as likely to develop dementia by the time they reached their 80s, compared with age-matched counterparts with no signs of amyloid accumulation. (auntminnie.com)
  • Higher magnification of Figure 1 with perivascular accumulation of amyloid (arrow). (nih.gov)
  • Widespread accumulation of amyloid with secondary tubular degeneration and necrosis. (nih.gov)
  • Our research was able to detect subtle thinking and memory differences in study participants and these participants had faster amyloid accumulation on brain scans over time, suggesting that amyloid may not necessarily come first in the Alzheimer's disease process," said study author Kelsey R. Thomas, PhD, of the VA San Diego Healthcare System in San Diego. (newswise.com)
  • After adjusting for age, education, sex, genetic risk for Alzheimer's disease, and amyloid level at the start of the study, researchers found people with subtle thinking and memory differences had a more rapid accumulation of amyloid compared to people with normal thinking and memory skills. (newswise.com)
  • On the other hand, researchers also found that, while people with mild cognitive impairment had more amyloid in their brains at the beginning of the study, they did not have faster accumulation of amyloid when compared to those with normal thinking and memory skills. (newswise.com)
  • Canadian researchers found that patients who took medications for vascular conditions, such as high cholesterol levels and blood pressure, had muted results on PET for beta-amyloid accumulation. (auntminnie.com)
  • Concurrently, vascular risk factors such as hypertension are believed to contribute to beta-amyloid accumulation and cardiovascular disease. (auntminnie.com)
  • The researchers, however, could find no statistically significant associations between vascular risk factors and beta-amyloid accumulation among the adults taking the medications. (auntminnie.com)
  • The research team found that amyloid accumulation was faster in persons classified with Obj-SCD than in the cognitively normal group. (ucsd.edu)
  • Persons with MCI had more amyloid in their brain at the start of the study, but they did not have faster accumulation of amyloid compared to those with normal cognition. (ucsd.edu)
  • The ability to identify those at risk for AD before significant impairment and before or during the phase of faster amyloid accumulation would be a clinical boon, said authors, providing both a way to monitor disease progression and a window of opportunity to apply potential preventive or treatment strategies. (ucsd.edu)
  • Fandrich M. On the structural definition of amyloid fibrils and other polypeptide aggregates. (medscape.com)
  • Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7-13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. (wikipedia.org)
  • One of the indications of AD is the presence of amyloid-β (Aβ) aggregates in the brains of those afflicted. (aiche.org)
  • The fact that these toxic amyloid aggregates have, until now, mainly been described in vitro , makes their identification and characterisation in affected brains one of the major challenges in amyloid research. (esrf.fr)
  • A team of researchers from Barcelona in collaboration with scientists from the ESRF have used infrared microscopy at beamline ID21 and at the ALBA synchrotron to characterise the amyloid aggregates in brain samples from patients in advanced stages of Alzheimer's disease. (esrf.fr)
  • Tau aggregates also have certain structural similarities to amyloid beta aggregates-yet any good tau tracer needs clearly to distinguish the one from the other. (dana.org)
  • Now, scientists report a molecular link between the two diseases in the form of protein aggregates known as amyloids. (scienceblog.com)
  • Natural tri- to hexapeptides self-assemble in water to amyloid β-type fiber aggregates by unexpected α-helical intermediate structures. (phys.org)
  • Many fatal neurodegenerative diseases such as Alzheimer s, Parkinson, the prion-related diseases, and non-neurodegenerative disorders such as type II diabetes are characterized by abnormal amyloid fiber aggregates, suggesting a common mechanism of pathogenesis. (phys.org)
  • One alternative explanation for the results is that the prion aggregates that cause CJD spurred the formation of amyloid-β plaques, a phenomenon called cross-seeding that has been shown in transgenic mice for aggregates of tau and α-synuclein . (the-scientist.com)
  • Scientists at IRB Barcelona in collaboration with researchers at the University of Barcelona observe that aggregates of 20 to 100 units of beta-amyloid have a structure that is the most harmful to neurons. (irbbarcelona.org)
  • We are blocking the actual production of beta-amyloid in a new way. (medicalnewstoday.com)
  • John Morris told MedPage Today that the evidence from past anti-amyloid drug trials had shown convincingly that, when symptoms have developed, it's too late to reverse them by shutting down further production of beta-amyloid protein. (medpagetoday.com)
  • The important question is what is the switch in healthy people which leads to the production of beta-amyloid and consequent neurodegeneration. (bio.net)
  • AD therapies need to deal with either preventing this switch and hence the production of beta-amyloid (which already successfully exist, through secretase inhibitors and knockout mice models), or by preventing the actions of beta-amyloid once produced (for example antioxidants show clinical benefits in AD). (bio.net)
  • We now have a new approach for the treatment of Alzheimer's disease that can arrest the production of beta amyloid very early and specifically," she said. (ucsd.edu)
  • The amyloid hypothesis has never been universally accepted, and the failed drug trials have only emboldened its critics. (nature.com)
  • Glenner thought that amyloid-β might be the cause of Alzheimer's disease, but the amyloid hypothesis did not take off until the discovery of the dominantly inherited mutations that are responsible for the familial forms of the condition. (nature.com)
  • What is the amyloid cascade hypothesis? (news-medical.net)
  • The amyloid cascade hypothesis was initially suggested in 1992. (news-medical.net)
  • Retrieved on December 09, 2019 from https://www.news-medical.net/life-sciences/Amyloid-Cascade-Hypothesis.aspx. (news-medical.net)
  • This is sure to disappoint researchers who have been hanging onto the "amyloid hypothesis" of Alzheimer's-the notion that amyloid-beta accumulating in the brain is what drives the disease. (forbes.com)
  • The fact that Expedition3 couldn't even replicate those hopeful findings from the two previous trials should raise questions about the amyloid hypothesis , says Michael Murphy, a professor at the Sanders-Brown Center on Aging at the University of Kentucky, and the author of an editorial that accompanies the study in the NEJM . (forbes.com)
  • While the results of Expedition3 were not what we had hoped they would be, we believe the amyloid hypothesis should continue to be studied," she said in an e-mailed statement. (forbes.com)
  • Even staunch advocates of the so-called amyloid hypothesis in Alzheimer's disease -- which holds that beta-amyloid protein plaques are a key causative factor in the neurodegeneration that underlies the condition -- had changed their thinking. (medpagetoday.com)
  • The working hypothesis is that the successful structure will incorporate the elements of an electron-donating group on an aromatic ring (A) attached to an aromatic heterocyclic 5/6 ring system (B/C). Eleven candidates will be synthesized and tested by in vitro homogenate displacement binding against radiolabeled ligand for amyloid protein. (sbir.gov)
  • Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. (nature.com)
  • It was another blow to the so-called amyloid hypothesis, which holds that Alzheimer's is the result of clumps of amyloid protein, called plaques, and that preventing their formation or clearing them from the brain might slow or even halt the decline. (xconomy.com)
  • The amyloid hypothesis or amyloid cascade model posits that accumulating amyloid protein plaques in the brain kill neurons and gradually impair specific cognitive functions, such as memory, resulting in AD dementia. (ucsd.edu)
  • However, many scientists are now questioning the amyloid hypothesis given the large number of clinical trials in which drugs targeted and successfully cleared amyloid from the brain but did not impact the trajectory of cognitive decline. (ucsd.edu)
  • [ 86 ] Whether causal or just associated, various autoimmune diseases can also predispose to the deposition of amyloid fibrils. (medscape.com)
  • Treatment of amyloid neuropathies is directed at both preventing further deposition of amyloid in peripheral nerves and treating painful symptoms. (hopkinsmedicine.org)
  • Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. (hindawi.com)
  • Amyloid goiter is clinically defined as the deposition of amyloid in the thyroid gland in such quantities as to produce an enlargement in the gland. (hindawi.com)
  • 2 , 3 Her FDG-PET scan (A) was incompatible with Alzheimer disease because of sparing of the cingulate gyri (arrows), but amyloid imaging (B) showed substantial diffuse fibrillary deposition of amyloid plaques throughout the brain, a pattern compatible with Alzheimer disease. (cmaj.ca)
  • For example, Biogen is currently testing a drug called aducanumab, which targets the insoluble form of amyloid-beta instead of the soluble form. (forbes.com)
  • Amyloid deposits are insoluble and can exert pressure on various vital organs. (encyclopedia.com)
  • The A4 protein accumulates extracellularly, both in brain parenchyma and in the walls of blood vessels, generally as amyloid plaques which form aggregate fibril structures and are insoluble on SDS-polyacrylamide gels. (google.com)
  • The drug is a monoclonal antibody that binds to solitary, soluble strands of beta-amyloid protein, causing it to be eliminated by the body's waste-clearance mechanisms before they aggregate into insoluble plaques. (medpagetoday.com)
  • Researchers proposed that when amyloid-β clumps together to form deposits in the brain, it triggers neurodegenerative processes that lead to the loss of memory and cognitive ability that is observed in Alzheimer's disease. (nature.com)
  • Yet amyloid-β is not the only potential cause, and some researchers think that it is time to explore alternative avenues. (nature.com)
  • UC Davis researchers have engineered other proteins so they spontaneously form amyloid. (eurekalert.org)
  • Researchers at UC Davis and Rice University have now come up with methods to manipulate natural proteins so that they self-assemble into amyloid fibrils. (eurekalert.org)
  • Most researchers now agree that beta amyloid buildup is most certainly involved in the disruption of memory and thought. (selfgrowth.com)
  • UCLA academic researchers are closer to explaining how vitamin D3 may help the body rid the brain of amyloid beta which is found in the plaques associated with Alzheimer's disease. (bellaonline.com)
  • Researchers have analysed Alzheimer's disease brain samples at beamlines ID21 and ID16A, utilising micro-FTIR and X-ray fluorescence microscopy to characterise two types of amyloid plaques with differences in metal ion composition and in their levels of oxidised lipids. (esrf.fr)
  • Combining infrared microscopy with X-ray fluorescence (XRF) measured at beamline ID16A allowed the researchers to study the correlation between different types of amyloid deposits and their metal ion composition ( Figure 1 ). (esrf.fr)
  • Researchers now broadly accept that its spreading dysfunction in the brain is more closely connected to the massive loss of neurons underlying dementia, compared to the early, slow buildup of amyloid beta plaques. (dana.org)
  • Because α-synuclein in melanoma cells may also be found in its soluble, or non-amyloid, form, the researchers performed other in vitro experiments in which they added soluble α-synuclein to the Pmel RPT domain. (scienceblog.com)
  • FLICKR, ALLAN AJIFO Examining the brains of recently deceased patients who more than 30 years ago received injections of growth hormone derived from the pituitary glands of cadavers, researchers have found evidence that Alzheimer's disease (AD) may be transmissible via extracts contaminated with amyloid-β. (the-scientist.com)
  • Subjects with amyloid-positive PET scans had a 2.3-fold increase in their risk of developing amnestic mild cognitive impairment, compared with those who had negative amyloid results, the researchers found. (auntminnie.com)
  • In a small pilot study, a team of US researchers has discovered how vitamin D3, a form of vitamin D, and omega 3 fatty acids may help the immune system clear the brain of amyloid plaques, one of the physical hallmarks of Alzheimer's disease. (medicalnewstoday.com)
  • In their earlier work, the researchers showed how certain mechanisms regulated by vitamin D3 help clear amyloid-beta, the abnormal protein found in sticky plaques that clog up the important communication space between brain cells in people with Alzheimer's. (medicalnewstoday.com)
  • The researchers incubated the macrophages for a few hours with amyloid beta. (medicalnewstoday.com)
  • Now in an Oct. 18 paper in Science , researchers led by Maiken Nedergaard, MD, of the University of Rochester Medical Center in New York, discovered a key reason why - during sleep the brain doubles the rate at which it removes metabolic debris, including amyloid-beta (Abeta). (lww.com)
  • Researchers at IRB Barcelona describe for the first time how to prepare a specific type of aggregate of the amyloid-beta protein with the ability to perforate the cell membrane. (irbbarcelona.org)
  • Researchers incubated the macrophages with amyloid beta, vitamin D3 and natural or synthetic curcumin. (emaxhealth.com)
  • In addition to cell culture experiments, researchers also conducted experiments with mice, engineered to produce large amounts of the human beta amyloid early in life. (ucsd.edu)
  • Perhaps most importantly, Köbe and colleagues noted that the findings could have "clinical implications," and that future researchers should be aware that "cardiovascular medication might reduce Alzheimer's risk by lowering arterial stiffness, leading to increased cerebral blood flow and [beta-amyloid] clearance. (auntminnie.com)
  • Since it offers a potentially faster and less expensive way to screen people for high amyloid burden than current tests, the researchers hope to make LASSI-L a low-tech tool to assist in medical evaluations and clinical trial recruitment. (nih.gov)
  • Writing in the December 30, 2019 online issue of Neurology , researchers at University of California San Diego School of Medicine and Veterans Affairs San Diego Healthcare System report that accumulating amyloid - an abnormal protein linked to neurodegenerative conditions such as Alzheimer's disease (AD) - occurred faster among persons deemed to have 'objectively-defined subtle cognitive difficulties' (Obj-SCD) than among persons considered to be 'cognitively normal. (ucsd.edu)
  • Familial amyloid polyneuropathy has an autosomal dominant pattern of inheritance. (wikipedia.org)
  • The medication tafamidis has been approved for the treatment of transthyretin familial amyloid polyneuropathy in Europe. (wikipedia.org)
  • The tetramer has to dissociate into misfolded monomers to aggregate into a variety of structures including amyloid fibrils. (wikipedia.org)
  • The fact that such plaques consist of amyloid-β, combined with the discovery of mutations that increase amyloid-β aggregation, strongly implicates amyloid-β as the culprit in familial Alzheimer's disease. (nature.com)
  • The aggregation of amyloid-β is thought to trigger a cascade of disease-causing processes such as inflammation, tau-tangle formation, synapse dysfunction and cell death, which ultimately leads to dementia. (nature.com)
  • This theory postulates that the initial event which triggers neuronal degradation in Alzheimer's disease is enhanced amyloid-β generation and aggregation. (news-medical.net)
  • These results help to elucidate the physics of the aggregation process, the chemistry of amyloid inhibitors, and the biology of type 2 diabetes, as well as clarify previously contradictory data. (redorbit.com)
  • We generated and analyzed 3,621 amino acid sequence patterns, reporting highly specific patterns for each amyloid family, along with patterns likely to be involved in protein misfolding and aggregation. (nih.gov)
  • Amyloid assembly into fibrils is initiated by a conformational transition from random coil to -sheet and a nucleation-dependent aggregation process. (anaspec.com)
  • We now have preliminary data that suggest an amyloid from one protein can 'seed' or template amyloid from another, and in the soluble form, α-synuclein prevents Pmel aggregation. (scienceblog.com)
  • This is the first time that a method allows scientists to monitor aggregation while simultaneously detect a structural pattern responsible for the toxicity of beta-amyloid aggregation. (irbbarcelona.org)
  • Together, these data imply a high-affinity cell-surface receptor for soluble amyloid-β oligomers on neurons-one that is central to the pathophysiological process in Alzheimer's disease. (nature.com)
  • Amyloid-β oligomers bind with nanomolar affinity to PrP C , but the interaction does not require the infectious PrP Sc conformation. (nature.com)
  • Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. (nature.com)
  • Synaptic targeting by Alzheimer's-related amyloid β oligomers. (nature.com)
  • Natural oligomers of the Alzheimer amyloid-β protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. (nature.com)
  • Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by clogging points of cell-cell contact. (ebi.ac.uk)
  • Amyloid diseases, such as Alzheimer's disease, type 2 diabetes, cataracts, and the spongiform encephalopathies, all share the common trait that proteins aggregate into long fibers which then form plaques. (redorbit.com)
  • Exebryl-1 has been shown to inhibit beta-amyloid protein aggregate formation in brain, as well as disaggregate amyloid plaques that are already present. (thefreedictionary.com)
  • When Dean added preformed α-synuclein amyloid to a test tube containing the amyloid-forming region of Pmel (known as the repeat, or RPT, domain), the α-synuclein fibrils stimulated Pmel to aggregate and form a twisted fibril structure that the protein does not normally adopt on its own. (scienceblog.com)
  • In this case, α-synuclein inhibited Pmel's ability to self-aggregate and form amyloid in a concentration-dependent manner. (scienceblog.com)
  • Molecules of beta amyloid naturally aggregate in a solution, as they appear to do in the brain. (medgadget.com)
  • But once the amyloids begin to aggregate into fibrils that resemble "microscopic strands of spaghetti," hydrophobic parts of the metal complex are naturally drawn to them. (medgadget.com)
  • The classical, histopathological definition of amyloid is an extracellular, proteinaceous fibrillar deposit exhibiting β-sheet secondary structure and identified by apple-green birefringence when stained with congo red under polarized light. (wikipedia.org)
  • Exactly what causes the brain to waste away in Alzheimer's disease is not clear, but scientists believe the abnormal amounts of faulty proteins in the form of amyloid plaques and tau tangles found in the brains of people who have died with the disease have something to do with it. (medicalnewstoday.com)
  • Amyloid: the Journal of Protein Folding Disorders is a peer-reviewed scientific journal that publishes original research and review articles on all aspects of the protein groups and associated disorders that are classified as amyloidoses as well as other disorders associated with abnormal protein folding. (wikipedia.org)
  • Then, controlling for age, we identified the effects of abnormal CSF amyloid-β42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. (gu.se)
  • Four years ago, Howard Hughes Medical Institute investigator David Eisenberg provided the first glimpse of the atomic structure of amyloid fibrils - long filaments of abnormal proteins stacked up inside cells. (emaxhealth.com)
  • β-amyloid protein has been found in the brains of Alzheimer's patients. (encyclopedia.com)
  • An amyloid that circulates in human blood and in cerebrospinal fluid and is deposited into plaques found in the brains of patients with Alzheimer's disease. (thefreedictionary.com)
  • Signs of the beta-amyloid protein were found in the brains of seven patients aged 36 to 51 who had died from Creutzfeldt-Jakob Disease (CJD) after receiving growth hormone from the pituitary glands of dead people. (thefreedictionary.com)
  • Amyloid and Alzheimer's disease: inside and out. (medscape.com)
  • Therefore, it has been suggested that boosting the non-toxic, non-amyloidogenic processing pathway or reducing the toxic amyloidogenic processing pathway may lead to less amyloid-β production and reduce the progression of Alzheimer's disease. (news-medical.net)
  • Amyloid proteins, for example, can self-assemble into the tangled plaques associated with Alzheimer's disease -- but similar proteins can also form very useful materials, such as spider silk, or biofilms around living cells. (eurekalert.org)
  • Fibrillogenesis of the amyloid β-protein (Aβ) is believed to play a central role in the pathogenesis of Alzheimer's disease. (pnas.org)
  • Two of the main isoforms, amyloid-beta40 (Abeta40) and amyloid-beta42 (Abeta42), are found prominently in the extracellular brain deposits associated with Alzheimer's disease (AD) [ PMID: 24312636 ]. (ebi.ac.uk)
  • A build-up of amyloid tissue in the brain is a feature of Alzheimer's disease , Creutzfeldt-Jakob disease , and bovine spongiform encephalopathy . (encyclopedia.com)
  • The present invention provides an in vitro tissue culture-based assay for amyloid deposition specific for Alzheimer's disease which is suitable for routine drug screening analysis. (google.com)
  • The failure of yet another anti-amyloid drug for Alzheimer's disease in phase III trials this summer turned out not to be the strategy's death knell after all. (medpagetoday.com)
  • Here's what's happened with drug development for Alzheimer's disease since we published the first 2012 piece on what appeared to be the demise of beta-amyloid as a drug target for symptomatic disease. (medpagetoday.com)
  • The March issue of the Journal of Alzheimer's Disease explains that vitamin D3 may trigger specific genes to set off cellular signaling which stimulates the immune system to clear away the dreaded amyloid-beta protein. (bellaonline.com)
  • A radiotracer that bound specifically to amyloid would be of great utility in diagnosis, monitoring treatment, and research of such Alzheimer's disease and related gerontological disorders. (sbir.gov)
  • Amyloid fibrils are found in more than 20 human diseases, including type II diabetes, Alzheimer's disease, Lou Gehrig's disease, and Creutzfeldt-Jakob disease ( CJD), the human version of mad cow disease. (emaxhealth.com)
  • In conclusion, the existence of amyloid deposits with disordered/non-fibrillar structure, coexisting with the typical fibrillary plaques, has been described for the first time in situ in human brains with advanced Alzheimer's disease. (esrf.fr)
  • A few months ago, experts were talking about the next generation of "disease-modifying" drugs that were expected to help treat Alzheimer's disease by attacking amyloid plaque in the brain. (ohsu.edu)
  • Amyloid" is the stuff that gets in the brain in Alzheimer's disease. (ohsu.edu)
  • The theory is that amyloid is toxic to the brain, setting up the slow burn we know as Alzheimer's disease. (ohsu.edu)
  • Thus, PrP C is a mediator of amyloid-β-oligomer-induced synaptic dysfunction, and PrP C -specific pharmaceuticals may have therapeutic potential for Alzheimer's disease. (nature.com)
  • SAN DIEGO, Calif, January 8, 2016 -- Investigators here have discovered that high sugar caused by Type 2 (adult-onset) diabetes and the beta-amyloid protein associated with Alzheimer's disease induce the same pathological modification on multiple enzymes in the brain. (thefreedictionary.com)
  • Beta-amyloid protein is the primary material found in the sticky brain "plaques" characteristic of Alzheimer's disease. (thefreedictionary.com)
  • Professor Martins is credited, in collaboration with Australian and German scientists, with isolating beta-amyloid protein , which forms amyloid plaque deposits in the brain, a characteristic diagnostic feature of Alzheimer's disease. (thefreedictionary.com)
  • Anti-amyloid drugs are considered "disease-modifying"-that is, they aim to fundamentally change the course of Alzheimer's disease. (xconomy.com)
  • The A4 study is a Phase III clinical trial for cognitively normal older adults whose brain scans show evidence of amyloid buildup, which places them at risk for memory loss and cognitive decline associated with Alzheimer's disease. (nih.gov)
  • April 30, 2018 -- The presence of amyloid on PET scans may be a sign that adults with no symptoms of dementia are still at risk of mild cognitive impairment or even Alzheimer's disease in the future as they age, according to a study published online April 30 in JAMA Neurology . (auntminnie.com)
  • There has been increasing evidence that elevated levels of amyloid in the brain are associated with an increased risk of Alzheimer's disease and could be the first preclinical sign of the illness. (auntminnie.com)
  • Beta-amyloid (A beta) plays a key role in the pathogenesis of Alzheimer's disease (AD) by inducing neurotoxicity and cell death mainly through production of reactive oxygen species (ROS). (wellnessresources.com)
  • Newswise - MINNEAPOLIS - The scientific community has long believed that beta-amyloid, a protein that can clump together and form sticky plaques in the brain, is the first sign of Alzheimer's disease. (newswise.com)
  • Much of the research exploring possible treatments for Alzheimer's disease has focused on targeting amyloid. (newswise.com)
  • UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer's disease. (emaxhealth.com)
  • The early research findings, which appear in the July issue of the Journal of Alzheimer's Disease, may lead to new approaches in preventing and treating Alzheimer's by utilizing the property of vitamin D3 - a form of vitamin D - both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta. (emaxhealth.com)
  • BACE1 finding reverses the formation of amyloid plaques in the mice who have Alzheimer's disease, opening a wide door for finding treatment for humans. (emaxhealth.com)
  • The presence of beta-amyloid plaque in certain brain regions is one of the telltale signs that a person might develop dementia or Alzheimer's disease. (auntminnie.com)
  • Genes that can cause neurofibrillary tangles and amyloid plaques are strongly associated with Alzheimer's disease. (dnalc.org)
  • The scans showed that those who had more semantic intrusions on the word test also had higher levels of the protein beta-amyloid that is associated with increased risk of mild cognitive impairment and developing Alzheimer's disease. (nih.gov)
  • Given the ability of amyloid fibrils to cross-seed the formation of chemically heterologous fibrils, the speculative etiologic role of dietary amyloid in other disease processes involving amyloid formation such as Alzheimer's disease and Type II Diabetes is also discussed. (environmental-expert.com)
  • Accumulating amyloid protein occurred faster among persons deemed to have 'objectively-defined subtle cognitive difficulties' than among persons considered to be 'cognitively normal,' offering potential new early biomarker for Alzheimer's disease. (ucsd.edu)
  • The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer's disease,' said senior author Mark W. Bondi, PhD, professor of psychiatry at UC San Diego School of Medicine and VASDSH. (ucsd.edu)
  • Because of its antioxidant properties, scientists at McGill University in Quebec have demonstrated (in tissue culture) that one form of gingko biloba can prevent the oxidative damage by beta amyloid. (selfgrowth.com)
  • In their previous laboratory work scientists were able to show that specific types of immune cells in Alzheimer's patients responded to therapy with vitamin D3 and curcumin, a chemical found in the spice known as turmeric to awaken the patient s own immune system to clear amyloid beta. (bellaonline.com)
  • Amyloid PET technology has made it easier for neurologists to diagnose difficult cases of dementia, and also has helped scientists understand how amyloid plaques accumulate during the disease process. (dana.org)
  • Encouraged by the amyloid imaging breakthrough, scientists around the world are now racing to develop them. (dana.org)
  • So the scientists of the world attacked amyloid with a vengeance, generating drugs to clamp down on the enzyme that produces it, on the process that causes it to crystallize in the brain, and developing synthetic antibodies designed to find and remove it like heat-seeking missiles. (ohsu.edu)
  • In both studies, scientists looked for signs of beta-amyloid protein , which forms clumps in the brains of Alzheimer's patients and is a key hallmark of the disease. (thefreedictionary.com)
  • However, scientists have evidence that the amyloid-forming protein is expressed more in melanoma cells than in healthy skin. (scienceblog.com)
  • Using blood samples from nine Alzheimer's patients, one patient with mild cognitive impairment and three healthy control subjects, scientists isolated monocyte cells, which transform into macrophages that act as the immune system's clean-up crew, traveling through the brain and body and gobbling up waste products, including amyloid beta. (emaxhealth.com)
  • Amyloid plaques are tell-tale protein deposits found abundantly in the brains of Alzheimer's patients. (eurekalert.org)
  • A big boost to Alzheimer's research in recent years has come from the invention of new tracer compounds for mapping amyloid beta plaques in the brains of living people. (dana.org)
  • Tau and amyloid tracers label distinct regions of Alzheimer's patients brains [Image courtesy of Neuron, Maruyama et al. (dana.org)
  • And this past August, they reported that the drugs did indeed lower the amounts of amyloid in the brains of living patients. (ohsu.edu)
  • Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. (nature.com)
  • This study will test whether an investigational drug, solanezumab, can slow the progression of memory problems associated with amyloid, a protein that forms plaques in the brains of people with Alzheimer disease. (nih.gov)
  • Can Amyloid Spread Between Brains? (the-scientist.com)
  • clumps of amyloid-β, known as plaques, that form outside cells, and strings of a protein called tau, known as neurofibrillary tangles, that form inside cells. (nature.com)
  • These aggregated proteins form protein clumps called amyloid deposits that accumulate in certain areas of the brain and in its blood vessels . (medlineplus.gov)
  • People who suffer from Alzheimer's more often have high levels of beta amyloid which collect in clumps, called senile plaques in the brain. (selfgrowth.com)
  • Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. (medlineplus.gov)
  • People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. (medlineplus.gov)
  • The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. (medlineplus.gov)
  • Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. (medlineplus.gov)
  • Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. (medlineplus.gov)
  • The drugmakers themselves have said that in 81 percent of the group taking the highest dose of BAN2401, the amount of amyloid plaque eliminated was enough to take early-stage Alzheimer's patients to a level below what would indicate dementia . (aarp.org)
  • The grant award for over $1,500,000 will continue to fund the development of a novel ophthalmic diagnostic compound for Cerebral Amyloid Angiopathy (CAA), an age-associated disease in which proteins called amyloid build up on the walls of the arteries in the brain increasing the risk for stroke caused by bleeding , and dementia . (globenewswire.com)
  • When better drugs become available, "amyloid imaging" could enable people to begin therapy in time to avoid or greatly delay Alzheimer's dementia. (dana.org)
  • A lot of elderly people show a high density of plaques on amyloid PET scans but don't develop dementia," says Neil Vasdev of Harvard Medical School. (dana.org)
  • In another case, an unexpectedly low level of tau labeling in one dementia patient led to the discovery that the man lacked signs of amyloid plaques too, and thus had likely been misdiagnosed with Alzheimer's. (dana.org)
  • Aducanumab, an antibody, clears away sticky beta-amyloid protein deposits in the brain that are linked to dementia. (thefreedictionary.com)
  • In Parkinson's disease, α-synuclein forms amyloid deposits that are thought to kill dopamine-producing neurons in the brain, causing symptoms such as tremor, slow movements and dementia. (scienceblog.com)
  • The same amyloid benchmark has been used to evaluate the risk of looming cognitive impairment and/or dementia in people with no signs of dementia. (auntminnie.com)
  • Despite this, there are relatively few population-based estimates of amyloid positivity in the population without dementia," the authors noted. (auntminnie.com)
  • Our first objective was therefore to estimate the prevalence of amyloid positivity in a population without dementia. (auntminnie.com)
  • A total of 1,671 participants (mean age, 71.3 ± 9.8 years) without dementia underwent amyloid PiB-PET imaging between August 2008 and September 2017. (auntminnie.com)
  • Despite the nonsignificant associations by sex for incident Alzheimer's dementia, the higher prevalence of amyloid positivity in women and sex differences in risk of progression for amyloid-positive individuals who are either cognitively unimpaired or have mild cognitive impairment may have implications for reporting clinical trial results by sex," the authors wrote. (auntminnie.com)
  • The build-up of beta amyloid plaques is widely believed to cause irreversible brain damage, resulting in a host of cognitive and motor impairments broadly associated with AD, which accounts for about 60 to 80 percent of all cases of dementia in the United States. (ucsd.edu)
  • It uses PET ligands that allow in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer disease (positive amyloid-β [Aβ] status). (cmaj.ca)
  • The second, A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's) is a solanezumab trial sponsored by Lilly that's investigating whether the drug can slow the onset of symptoms in people who have evidence of amyloid deposits in their brain. (forbes.com)
  • A confirmed diagnosis of CAA can only be made on the basis of biopsy or autopsy evidence of amyloid deposits in the cerebral blood vessels. (aerzteblatt.de)
  • It was initially described in 1907 by Dr. Alois Alzheimer when he noticed amyloid plaques in the brain of Auguste Deter, a patient with several cognitive impairment. (news-medical.net)
  • The latest study of a drug designed to clear amyloid deposits in the brain raises questions about whether focusing on the plaque-forming protein makes a difference in treating Alzheimer's. (forbes.com)
  • The hope was that if the drug could eliminate soluble amyloid-beta-the protein blamed for the brain plaques that form in patients-Alzheimer's progression might be stopped, or at least slowed significantly. (forbes.com)
  • Because we now know that amyloid builds up in the brain 15-20 years before symptoms, the broader scientific community has hypothesized that Alzheimer's may need to be targeted earlier in the disease progression. (forbes.com)
  • An early trial of the drug detailed in a 2016 paper in the journal Nature did indicate that in patients with a mild form of Alzheimer's, one month of treatment reduced levels of amyloid-beta in the brain and slowed the rate of cognitive decline . (forbes.com)
  • The effect of the buildup of beta amyloid in the brain, caused by a variation of a gene known as CYP46, is memory loss better known as Alzheimer's. (selfgrowth.com)
  • Excessive buildup of beta amyloid is also associated with high levels of cholesterol in the brain. (selfgrowth.com)
  • Cerebral amyloid angiopathy (CAA) is characterized histopathologically by amyloid fibrils in the small to middle-sized blood vessels usually the arteries of the brain. (aerzteblatt.de)
  • Other development programs include the detection of Cerebral Amyloid Angiopathy, Creutzfeldt-Jakob disease, and Traumatic Brain Injury, all of which are associated with the presence of amyloid proteins. (globenewswire.com)
  • Abstract DESCRIPTION (provided by applicant): The goal of this research project is to define the structure and radioactive label for ligands that will per-mit quantitative measurement of amyloid sites in living brain by external imaging with positron (PET) or single photon (SPECT) emission tomography. (sbir.gov)
  • Designed for use with positron emission tomography (PET) scanners, the new tracers are injected into the bloodstream and cross quickly into the brain, where they preferentially bind to amyloid plaques, and mark them-briefly-with emissions of mild radioactivity. (dana.org)
  • One of their better optimized compounds, THK-5105, labels the usual brain regions that are hit by tau pathology, and doesn't label amyloid beta deposits, in Alzheimer's brain slices as well as in living patients. (dana.org)
  • This is amazing all by itself when you consider that extracting amyloid from brain tissue at autopsy requires concentrated acid and worse. (ohsu.edu)
  • There was less amyloid in the brain, but the brain did not work any better. (ohsu.edu)
  • A specific amyloid-β protein assembly in the brain impairs memory. (nature.com)
  • All volunteers will undergo a positron emission tomography (PET) scan to be determine their brain amyloid levels. (nih.gov)
  • The study will test the safety and efficacy of solanezumab, a monoclonal antibody, to see if it slows memory and cognitive decline and affects the buildup of amyloid plaques, as shown by brain imaging and other biomarkers. (nih.gov)
  • What we find, very much to our surprise, is that, of these eight patients, four of them had quite significant and quite severe deposition of Alzheimer's amyloid protein in their brain," Collinge said. (the-scientist.com)
  • There is very strong evidence coming from transgenic mice experiments that these things can happen in experimental models," Soto said, noting that his group and others have induced amyloid-β deposition in mice by injecting brain extracts from an AD patient. (the-scientist.com)
  • The investigators have preliminary evidence that selective serotonin reuptake inhibitor (SSRI) antidepressants lower the amount of amyloid plaques in the human brain. (clinicaltrials.gov)
  • Beta-amyloid then leads to other brain changes including neurodegeneration and eventually to thinking and memory problems. (newswise.com)
  • The study suggests that subtle thinking and memory differences may come before, or happen alongside, the development of amyloid plaques that can be detected in the brain. (newswise.com)
  • Participants had brain scans at the start of the study to determine levels of amyloid plaques in the brain, and then yearly scans for four years. (newswise.com)
  • It is also possible that the earliest stages of amyloid plaques forming in the brain are not detectable with brain scans. (newswise.com)
  • Conversely, individuals who were not on vascular medication exhibited greater levels of several vascular risk factors, as well as increased beta-amyloid deposition in the brain. (auntminnie.com)
  • A simple and inexpensive word recall test accurately predicted whether people had elevated brain levels of beta-amyloid. (nih.gov)
  • The LASSI-L also helped sort out these people from individuals who showed clinical symptoms of mild cognitive impairment but had negative amyloid scans and people who were diagnosed with non-Alzheimer's brain disorders that impacted cognition. (nih.gov)
  • The new findings, say authors, suggest that Obj-SCD can be detected during the preclinical state of AD when amyloid plaques are accumulating in the brain, neurodegeneration is just starting, but symptoms of impairment on total scores on thinking and memory tests have not yet been recorded. (ucsd.edu)
  • A rendering of amyloid protein plaques accumulating between neurons in the brain. (ucsd.edu)
  • A phase I study showed that MK-8931 reduced beta-amyloid protein levels in cerebrospinal fluid by more than 90% in healthy individuals. (medpagetoday.com)
  • Our estimates of progression [from] amyloid-positive, cognitively unimpaired status to amnestic mild cognitive impairment may provide reliable and valid information from a population-based study for estimating the outcome of a successful antiamyloid therapeutic agent on a general North American population," wrote lead author Dr. Rosebud Roberts and colleagues. (auntminnie.com)
  • Although we did not find a significant interaction of amyloid positivity with sex, higher rates of progression in amyloid-positive women with mild cognitive impairment compared with men may be partly because of the higher prevalence of amyloid positivity in women. (auntminnie.com)
  • The study gave the first evidence that semantic errors on cognitive tests like the LASSI-L were more common in people with mild cognitive impairment who were beta-amyloid positive. (nih.gov)
  • Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment. (nih.gov)
  • Unlike phase one results in December 2017, which showed disappointing results after 12 months, this phase - which lasted 18 months - showed how the drug not only cleared out significant amounts of amyloid plaque (a hallmark of the disease) but also seemed to slow the progression of the disease by 30 percent. (aarp.org)
  • The nano-XRF distribution maps show that zinc and copper clearly co-localise with the amyloid deposits, while iron appears to be associated with the plaque border ( Figure 2 ). (esrf.fr)
  • As for the different types of amyloid plaque, the concentration of iron was found to be higher in fibrillary plaques than in non-fibrillary ones, whereas the levels of copper and zinc were found to be similar in both types of amyloid deposits. (esrf.fr)
  • A third team, from Avid Radiopharmaceuticals-developer of one of the existing amyloid plaque tracers-has described successful early tests of their new tau tracer compounds T807 and T808. (dana.org)
  • The mutations favour the production of longer variants of amyloid-β that clump together more readily. (nature.com)
  • Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. (medlineplus.gov)
  • A. Abedini and D. P. Raleigh, "Destabilization of human IAPP amyloid fibrils by proline mutations outside of the putative amyloidogenic domain: is there a critical amyloidogenic domain in human IAPP? (hindawi.com)
  • While amyloid-β is not uncommon among the elderly, the patients examined in this study were only 36 to 51 years old when they died, and none had mutations that would predispose them to early-onset AD. (the-scientist.com)
  • There are many different types of hereditary cerebral amyloid angiopathy. (medlineplus.gov)
  • The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed. (medlineplus.gov)
  • The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. (medlineplus.gov)
  • The prevalence of hereditary cerebral amyloid angiopathy is unknown. (medlineplus.gov)
  • Lefterov I, Fitz NF, Cronican AA, Fogg A, Lefterov P, Kodali R, Wetzel R, Koldamova R . Apolipoprotein A-I deficiency increases cerebral amyloid angiopathy and cognitive deficits in APP/PS1DeltaE9 mice . (alzforum.org)
  • Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy that is classically associated with lobar intracerebral or sulcal hemorrhage. (aerzteblatt.de)
  • This review is based on pertinent publications retrieved by a selective search employing the terms amyloid cerebral angiopathy, stroke, intracerebral bleeding, and acute stroke therapy. (aerzteblatt.de)
  • These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. (gu.se)
  • Fandrich M, Meinhardt J, Grigorieff N. Structural polymorphism of Alzheimer Abeta and other amyloid fibrils. (medscape.com)
  • We are working on building high-resolution predictions for medically relevant amyloids, starting with the Alzheimer\'s-beta fragment (1-40). (bakerlab.org)
  • This process, called amyloid formation, is a common pathological feature in diseases such as Alzheimer s, Parkinson s and prion diseases, as well as type II diabetes. (phys.org)
  • The classic "shoulder-pad" sign denotes end-stage amyloid deposits in the shoulder synovium and periarticular structures, but is rarely seen. (medscape.com)
  • These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes inhomogeneous structures. (wikipedia.org)
  • Furthermore, bacteria have mechanisms to produce functional amyloid structures with important roles in bacterial physiology and interaction with host cells. (nih.gov)
  • However, recent data show that HD6 can form amyloid structures at the gut mucosa with strong affinity for bacterial surfaces. (nih.gov)
  • Eisenberg's earlier work on fibrils led to his discovery of steric zippers, and in new work published August 16, 2009, in Nature Structural & Molecular Biology, he adds more zipper patterns to the catalogue of possible amyloid structures. (emaxhealth.com)
  • Why predict amyloid structures? (bakerlab.org)
  • Amyloids adopt 'cross-β' structures composed of long, twisted fibrils with β-strands running perpendicular to the fibril axis. (rcsb.org)
  • We have discovered that a class of systematically designed natural tri- to hexapeptides with a characteristic sequential motif can simulate the process of fiber assembly and further condensation to amyloid fibrils, probably via unexpected dimeric α-helical intermediate structures. (phys.org)
  • Plaques form when protein pieces called beta-amyloid (BAY-tuh AM-uh-loyd) clump together. (alz.org)
  • The question is: Do these types of vascular medications really provide a deterrent to beta-amyloid buildup? (auntminnie.com)
  • [ 5 ] In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. (medscape.com)
  • One of these factors is the ordered accumulations of misfolded proteins called amyloid fibrils. (asbmb.org)
  • The mechanism(s) responsible for islet amyloid formation in type 2 diabetes is still unclear but it appears that an increase in the secretion of IAPP, per se, is not sufficient. (nih.gov)
  • Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species," FEBS Letters , vol. 251, no. 1-2, pp. 261-264, 1989. (hindawi.com)
  • And even if the evidence that anti-amyloid strategies may fend off Alzheimer's is strong, actually developing the drugs for that purpose will prove challenging, Murphy predicts. (forbes.com)
  • Well, it means either that amyloid is not the problem after all, or it means that anti-amyloid strategies have to be started earlier in the game in order to be clinically useful. (ohsu.edu)
  • How are the results of the amyloid fibril structure prediction coming? (bakerlab.org)
  • To date, 37 human proteins have been found to form amyloid in pathology and be associated with well-defined diseases. (wikipedia.org)
  • Amydis, Inc., founded in 2013, is a privately-held company discovering novel small molecule drugs to allow direct visualization of CNS molecular pathology through the retina to detect, monitor, and screen diseases that involve the presence of amyloid proteins. (globenewswire.com)
  • It's the first in-human indication of potential transmission of amyloid-β pathology," said Claudio Soto of the University of Texas Health Science Center in Houston who was not involved in the study. (the-scientist.com)
  • And while it is atypical to see amyloid-β pathology in people this young, it is not unheard of , Trojanowski added. (the-scientist.com)
  • In the human body, amyloids have been linked to the development of various diseases. (wikipedia.org)
  • BMC is an international referral center for the diagnosis and treatment of systemic amyloid diseases. (bmc.org)
  • SAN DIEGO, Sept. 23, 2019 (GLOBE NEWSWIRE) -- Amydis, Inc., a privately-held pharmaceutical company developing proprietary drugs to detect, monitor, and screen for amyloid-related diseases, announced today that they received a Phase 2A SBIR grant award from the National Institute on Aging of the National Institutes of Health (NIH). (globenewswire.com)
  • Amydis has a platform of novel compounds that fluoresce when bound to amyloid-related proteins, thus enabling visual diagnosis of such diseases. (globenewswire.com)
  • Most people know that amyloids are involved in diseases, such as Parkinson's and Alzheimer's, but it's less well-known that some amyloids, like Pmel, actually serve a useful function," Lee says. (scienceblog.com)
  • [ 2 ] Many classic eponymic diseases were later found to be related to a diverse array of misfolded polypeptides (amyloid) that contain the common beta-pleated sheet architecture. (medscape.com)
  • CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. (ebi.ac.uk)
  • Current diagnosis of CAA involves expensive imaging tests such as MRI, CT scans, and PET amyloid tests. (globenewswire.com)
  • Subjects had their first PET amyloid scans beginning in 2008 with four five-minute exams acquired 40 to 60 minutes after injection of PiB. (auntminnie.com)
  • Amyloid positivity was based standardized uptake value ratios (SUVRs) greater than 1.42 on the PET scans. (auntminnie.com)
  • February 12, 2020 -- Patients who were on cardiovascular medications like cholesterol-lowering drugs seem to have lower levels of amyloid burden on PET scans, according to a study published February 7 in JAMA Network Open . (auntminnie.com)
  • Instead, anti-amyloid drugs would be effective only if introduced much earlier in the disease process, before plaques have become extensive and before neurodegeneration has really taken hold. (medpagetoday.com)
  • I would say that neurodegeneration in Alzheimers mouse models was a beta- amyloid thing! (bio.net)