Amyloid: 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.Amyloid beta-Peptides: 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.Serum Amyloid A Protein: 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.Amyloid beta-Protein Precursor: 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.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Islet Amyloid Polypeptide: 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.Amyloidosis: 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.Cerebral Amyloid Angiopathy: 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)Serum Amyloid P-Component: 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.Amyloid Neuropathies: 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)Amyloid Precursor Protein Secretases: 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.Alzheimer Disease: 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)Congo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.Amyloid Neuropathies, Familial: 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.Prealbumin: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Presenilin-1: 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.ThiazolesMice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Brain: 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.Cerebral Amyloid Angiopathy, Familial: A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.Prions: 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.Protein Structure, Secondary: 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.Amyloidosis, Familial: Diseases in which there is a familial pattern of AMYLOIDOSIS.Neurofibrillary Tangles: 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.Amino Acid Sequence: 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.tau Proteins: 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).Molecular Sequence Data: 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.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Microscopy, Atomic Force: 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.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.beta 2-Microglobulin: 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.Aniline CompoundsNeurons: 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.Disease Models, Animal: 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.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Circular Dichroism: 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)Insulysin: 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 3.4.24.56.Microscopy, Electron: 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.Protein Conformation: 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).Presenilin-2: 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.Protein Binding: 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.Mutation: 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, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Protein Structure, Tertiary: 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.Alzheimer Vaccines: Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Peptides: 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.Hippocampus: 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.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Cerebral Cortex: 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.Spectroscopy, Fourier Transform Infrared: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Neurofibrils: 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.Mice, Inbred C57BLApolipoproteins E: 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.Gerstmann-Straussler-Scheinker Disease: 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)Peptide Termination Factors: 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.Apolipoprotein E4: 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.Microglia: 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.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Cells, Cultured: 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.Presenilins: 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.Kinetics: The rate dynamics in chemical or physical systems.Neurodegenerative Diseases: 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.Receptors, Islet Amyloid Polypeptide: 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.Nerve Tissue ProteinsNeprilysin: 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.Islets of Langerhans: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Protein Processing, Post-Translational: 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.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.Positron-Emission Tomography: 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.Acute-Phase Reaction: 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.PC12 Cells: 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.Nuclear Magnetic Resonance, Biomolecular: 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.Maze Learning: 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)Enzyme-Linked Immunosorbent Assay: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Solubility: 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)Trifluoroethanol: A non-aqueous co-solvent that serves as tool to study protein folding. It is also used in various pharmaceutical, chemical and engineering applications.Prion Diseases: 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)Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Coloring Agents: Chemicals and substances that impart color including soluble dyes and insoluble pigments. They are used in INKS; PAINTS; and as INDICATORS AND REAGENTS.Benzothiazoles: Compounds with a benzene ring fused to a thiazole ring.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Membrane Proteins: 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.Brain Chemistry: 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.Cell Line: 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)

*Serum amyloid A1

"Serum amyloid A binding to CLA-1 (CD36 and LIMPII analogous-1) mediates serum amyloid A protein-induced activation of ERK1/2 ... "Transformation of amyloid precursor SAA to protein AA and incorporation in amyloid fibrils in vivo". Scandinavian Journal of ... Serum amyloid A1 (SAA1) is a protein that in humans is encoded by the SAA1 gene. SAA1 is a major acute-phase protein mainly ... Sun L, Zhou H, Zhu Z, Yan Q, Wang L, Liang Q, Ye RD (May 2015). "Ex vivo and in vitro effect of serum amyloid a in the ...

*AA amyloidosis

Kiacta, inhibits the formation and deposition of the amyloid A fibrils into the tissues. There is evidence that eating amyloid ... Nevertheless, because amyloid fibers can be detected in muscle in low amounts, it raises some concern about whether people ... In AA amyloidosis, the deposited protein is serum amyloid A protein (SAA), an acute-phase protein which is normally soluble and ... "AA Amyloidosis". BU Amyloid Treatment & Research Program. Daisuke Katagiri; Eisei Noiri; Fumihiko Hinoshita (2013). "Multiple ...

*Familial renal amyloidosis

"Amyloid". Gillmore JD, Lachmann HJ, Rowczenio D, Gilbertson JA, Zeng CH, Liu ZH, Li LS, Wechalekar A, Hawkins PN (2009). " ... Familial renal amyloidosis (or familial visceral amyloidosis, or hereditary amyloid nephropathy) is a form of amyloidosis ... 56: 253-4. Ostertag, B. (1950). "Familiaere Amyloid-erkrankung". Z. Menschl. Vererb. Konstitutionsl. 30: 105-115. ... Amyloid. 5 (3): 188-92. doi:10.3109/13506129809003844. PMID 9818055. Soutar AK, Hawkins PN, Vigushin DM, et al. (August 1992 ...

*Wild-type transthyretin amyloid

... (WTTA), also known as senile systemic amyloidosis (SSA) and abbreviated as ATTR, is a disease ... Wild-type transthyretin amyloid accumulates mainly in the heart, where it causes stiffness and often thickening of its walls, ... Some patients may develop carpal tunnel syndrome as an initial symptom of wild-type transthyretin amyloid. There appears to be ...

*Amyloid beta

... may be primarily vascular, as in cerebral amyloid angiopathy, or in senile plaques in white matter. One sensitive ... By NMR-guided simulations, amyloid beta 1-40 and amyloid beta 1-42 also seem to feature highly different conformational states ... Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ... Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are crucially involved in Alzheimer's disease as the main ...

*Amyloid precursor protein

Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause ... Zheng H, Koo EH (2006). "The amyloid precursor protein: beyond amyloid". Molecular Neurodegeneration. 1 (1): 5. doi:10.1186/ ... whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. ... "Pathogenic effects of cerebral amyloid angiopathy mutations in the amyloid beta-protein precursor". Annals of the New York ...

*Alzheimer's disease research

Palmqvist, Sebastian (Oct 2014). "Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid β-amyloid ... It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide. Negative results ... One approach is to reduce amyloid beta, for example with bapineuzumab, an antibody in phase III studies for patients in mild to ... The most widely used biomarker is the peptide beta-amyloid 1-42 (Aβ42), which is measured in cerebrospinal fluid. Levels of A ...

*SAA2

"Entrez Gene: SAA2 Serum amyloid A2". Betts JC, Edbrooke MR, Thakker RV, Woo P (1991). "The human acute-phase serum amyloid A ... Serum amyloid A protein is a protein that in humans is encoded by the SAA2 gene. GRCh38: Ensembl release 89: ENSG00000134339 - ... One serum amyloid A isotype is selectively removed from the circulation". J. Exp. Med. 163 (3): 499-510. doi:10.1084/jem.163.3. ... 1990). "Serum amyloid A, an acute phase protein, inhibits platelet activation". J. Lab. Clin. Med. 116 (2): 180-6. PMID 1697614 ...

*Transthyretin

... and familial amyloid cardiomyopathy (FAC). TTR tetramer dissociation is known to be rate-limiting for amyloid fibril formation ... Deposition of TTR amyloid is generally observed extracellularly, although TTR deposits are also clearly observed within the ... TTR is also thought to have beneficial side effects, by binding to the infamous beta-amyloid protein, thereby preventing beta- ... Treatment of familial TTR amyloid disease has historically relied on liver transplantation as a crude form of gene therapy. ...

*Amyloid

Inclusion Bodies Contain Amyloid-Like Structure at SciVee Amyloid Cascade Hypothesis Stanford University Amyloid Center Amyloid ... The "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built ... The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or amylin. This ... In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously ...

*Amyloid cardiomyopathy

It can be characterized by the extracellular deposition of amyloid in the heart. Amyloids are foldable proteins that all stick ... Amyloid cardiomyopathy (stiff heart syndrome) is associated with the systemic production and release of many amyloidogenic ... Liao, Ronglih; Ward, Jennifer E. (2017-06-09). "Amyloid Cardiomyopathy: Disease on the Rise". Circulation Research. 120 (12): ... Falk, Rodney H.; Dubrey, Simon W. (2010-01-01). "Amyloid Heart Disease". Progress in Cardiovascular Diseases. Unusual ...

*Amyloid purpura

Amyloid deposits in the gastrointestinal tract and liver may also play a role in the development of amyloid purpura. Amyloid ... Its cause is unknown, but coagulation defects caused by amyloid are thought to contribute. Amyloid purpura usually occurs above ... Amyloid purpura". N. Engl. J. Med. 356 (23): 2406. doi:10.1056/NEJMicm061510. PMID 17554122. Gamba G, Montani N, Anesi E, et al ... Amyloid purpura is a condition marked by bleeding under the skin (purpura) in some individuals with amyloidosis. ...

*Amyloid (journal)

"Amyloid, The ISA Journal". amyloidosis.nl. "Journal Citation Reports". Clarivate Analytics. Retrieved 2017-12-18. "Amyloid, The ... Amyloid: the Journal of Protein Folding Disorders is a peer-reviewed scientific journal that publishes original research and ... Alan Cohen was the founding editor and from 1994 until 2010 the first Editor-in-Chief of Amyloid: The Journal of Protein ... The present editor in chief is Per Westermark (Uppsala University, Sweden). "Amyloid-Aims and Scope". informahealthcare.com. " ...

*Amyloid (disambiguation)

An amyloid is any of certain insoluble fibrous protein aggregates. Amyloid may also refer to: Amyloid (mycology), a chemical ... reaction used in characterization of fungi Amyloid (journal), the Amyloid: the Journal of Protein Folding Disorders peer- ...

*Amyloid (mycology)

In mycology a tissue or feature is said to be amyloid if it has a positive amyloid reaction when subjected to a crude chemical ... The term "amyloid" is derived from the Latin amyloideus ("starch-like"). It refers to the fact that starch gives a similar ... reaction, also called an amyloid reaction. The test can either be on microscopic features, such as spore walls or hyphal walls ...

*Familial amyloid neuropathy

"Amyloid". "Amyloid". Akiya S, Nishio Y, Ibi K, et al. (July 1996). "Lattice corneal dystrophy type II associated with familial ... The familial amyloid neuropathies (or familial amyloidotic neuropathies, neuropathic heredofamilial amyloidosis, familial ... Hammarström P, Wiseman RL, Powers ET, Kelly JW (January 2003). "Prevention of transthyretin amyloid disease by changing protein ... July 2006). "Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy". Medicine ( ...

*Familial amyloid cardiomyopathy

... (FAC), or Transthyretin Amyloid Cardiomyopathy (ATTR-CM) results from the aggregation and ... Transthyretin cardiac amyloid study (TRACS). Circ.: Heart Failure 4, 121-128. Miller, A. L., Falk, R. H., Levy, B. D. & ... Amyloid 10 Suppl 1, 48-54. Falk, R. H. & Elkayam, U. (2010). Cardiomyopathy: the importance of recognizing the uncommon ... TTR amyloid fibrils infiltrate the myocardium, leading to diastolic dysfunction from restrictive cardiomyopathy, and eventual ...

*Cerebral amyloid angiopathy

... (CAA), also known as congophilic angiopathy, is a form of angiopathy in which amyloid deposits form ... The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis. Since ... Mutations in the amyloid precursor protein (APP), Presenilin (PS) 1 and PS2 genes can result in increased rates of cleavage of ... "Cerebral amyloid angiopathy: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-05-27. Exley C, Esiri MM (July ...

*Serum amyloid A

... (SAA) is also an acute phase marker that responds rapidly. Similar to CRP, levels of acute-phase SAA increase ... Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. These proteins have several ... Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. ... de Beer MC; Kindy MS; Lane WS; de Beer FC (1994). "Mouse serum amyloid A protein (SAA5) structure and expression". J. Biol. ...

*Amyloid-related imaging abnormalities

"Amyloid Related Imaging Abnormalities (ARIA) in Amyloid Modifying Therapeutic Trials: Recommendations from the Alzheimer's ... Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in neuroimaging of Alzheimer's Disease patients, ... "Paris: Renamed ARIA, Vasogenic Edema Common to Anti-Amyloid Therapy , ALZFORUM". www.alzforum.org. Retrieved 2016-12-11. ... DiFrancesco, Jacopo C.; Longoni, Martina; Piazza, Fabrizio (2015-09-25). "Anti-Aβ Autoantibodies in Amyloid Related Imaging ...

*Amyloid precursor protein secretase

If α-secretase acts on APP first instead of BACE, no amyloid-β is formed because α-secretase recognizes a target protein ... Among other roles in the cell, secretases act on the amyloid precursor protein (APP) to cleave the protein into three fragments ... Sequential cleavage by β-secretase (BACE) and γ-secretase produces the amyloid-β peptide fragment that aggregates into clumps ...

*Serum amyloid P component

The serum amyloid P component (SAP) is the identical serum form of amyloid P component (AP), a 25kDa pentameric protein first ... The SAP-amyloid association has also been identified as a possible drug target for anti-amyloid therapy, with the recent ... Tennent GA, Lovat LB, Pepys MB (May 1995). "Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer ... "Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene". Nature Medicine. 3 (8): ...

*Hereditary cystatin C amyloid angiopathy

... (HCCAA) is a rare, fatal amyloid disease in young people in Iceland caused by a ... "Hereditary cystatin C amyloid angiopathy: genetic, clinical, and pathological aspects". Brain Pathol. 16 (1): 55-9. Jan 2006. ... Levy, E; Jaskolski, M; Grubb, A (January 2006). "The role of cystatin C in cerebral amyloid angiopathy and stroke: cell biology ... Levy E, Lopez-Otin C, Ghiso J, Geltner D, Frangione B (May 1989). "Stroke in Icelandic patients with hereditary amyloid ...

*Bence Jones protein

December 2005). "Quantitative serum free light chain assay in the diagnostic evaluation of AL amyloidosis". Amyloid. 12 (4): ...

*Proteopathy

In addition, apolipoprotein AII amyloid can be induced in mice by a variety of β-sheet rich amyloid fibrils, and cerebral ... Subsequent research has shown that many different proteins can form amyloid, and that all amyloids have in common birefringence ... 2007). "Induction of Tau Pathology by Intracerebral Infusion of Amyloid-β-Containing Brain Extract and by Amyloid-β Deposition ... 2007). "A primer of amyloid nomenclature". Amyloid. 14 (3): 179-183. doi:10.1080/13506120701460923. PMID 17701465. Westermark, ...
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 ...
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 ...
Misfolded β-sheet structures of proteins leading to neurodegenerative diseases like Alzheimers (AD) and Parkinsons diseases (PD) are in the spotlight since long. However, not much was known about the functional amyloids till the last decade. Researchers have become increasingly more concerned with the degree of involvement of these functional amyloids in human physiology. Interestingly, it has been found that the human body is exposed to a tremendous systemic amyloid burden, especially, during aging. Though many findings regarding these functional amyloids come up every day, some questions still remain unanswered like do these functional amyloids directly involve in the fibrillization of Amyloid beta (Aβ) 42 peptide or enhance the Aβ42 aggregation rate; whether functional bacterial amyloids (FuBA) co-localize with the senile plaques of AD or not ...
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 ...
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 ...
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. ...
phdthesis{f475f263-31b6-4989-81bd-1aa466807429, abstract = {Several neurodegenerative diseases are caused by peptides or proteins forming amyloid fibrils such as the Aβ peptide involved in Alzheimers disease and the huntingtin exon-1 with a prolonged polyglutamine (polyQ) stretch involved in Huntingtons disease. The ability to form amyloid fibrils is an intrinsic feature in all proteins. The fibrils are built up of monomers to form elongated structures with β-sheets perpendicular to the fiber axis. Molecular chaperones are involved in maintaining the protein homeostasis in the cells, in preventing protein aggregation, in refolding misfolded proteins and in mediating degradation of proteins and also in preventing amyloid fibril formation. DNAJB6 is a member of the HSP40 chaperone family, and has been found to be superior compared to other chaperones in its ability to prevent aggregation of huntingtin exon-1 in human cells. In this thesis we have expressed and purified DNAJB6 in order to ...
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 ...
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 fibrils are associated with a range of highly debilitating neurological disorders including Alzheimers disease, Parkinsons disease and the spongiform encephalopathies. These structures are formed by the misfolding and self-assembly of peptides and proteins varying widely in sequence and in native conformation. Here we combine experimental measurements derived from sold-state NMR, X-ray fibre diffraction and Atomic Force Microscopy to determine the complex, higher order protofilament structure adopted by an 11-amino acid peptide fragment of the human plasma protein transthyretin, TTR(105-115). This determination of the structure of amyloid fibrils to atomic resolution is crucial to the understanding of non-native protein self-assembly and the molecular basis of protein deposition diseases. We then demonstrate that amyloid fibrils, ordered supramolecular structures that we self-assemble from a wide range of polypeptide molecules, constitute a class of high-performance biomaterials and ...
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., ...
There is compelling evidence supporting amyloid as one of the key pathologic agents in AD. Autopsy studies suggest the amount and location of fibrillar amyloid deposition does not relate strongly to the degree and type of clinical impairment, compared to tau pathology and neuronal loss. A substantial percentage of individuals known to be cognitively intact prior to death demonstrate significant amyloid pathology at autopsy. PIB-PET studies of older normal individuals have also demonstrated significant amyloid deposition in substantial percentages.. This study will test the hypothesis that amyloid is associated with synaptic dysfunction and neuronal damage. While some individuals are able to compensate for amyloid-related toxicity for an extended time period, sensitive imaging and neuropsychological markers will reveal that normal subjects with evidence of high amyloid burden do demonstrate evidence of abnormality consistent with prodromal AD.. The study will use a combination of functional, ...
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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
Abstract: In Alzheimers disease, the neuritic or senile amyloid plaques in hippocampus and association cortex, the diffuse plaques in brain areas such as the cerebellum and sensorimotor cortex, and the amyloid deposits in the walls of pial and parenchymal blood vessels are mainly composed of amyloid β-peptides. In the present study, either soluble 40-residue amyloid β-peptide radiolabeled with 125I (I-sAβ) or [14C]polyethylene glycol ([14C]-PEG, a reference material) was briefly infused into one lateral ventricle of normal rats. By 3.5 min, 30% of the I-sAβ was cleared from ventricular CSF into blood; another 30% was removed over the next 6.5 min. No [14C]PEG was lost from the CSF-brain system during the first 5 min, and only 20% was cleared by 10 min. Much of the I-sAβ that reached the subarachnoid space was retained by pial arteries and arterioles. Virtually no I-sAβ was found in brain. The clearance of amyloid β-peptides from the CSF-brain system, reported herein for normal rats, may ...
Serum amyloid A (SAA) is a major acute phase reactant and a small apolipoprotein of high density lipoproteins (HDL) in the serum. In cases of prolonged inflammation, SAA may form amyloid fibrils, leading to the disease of amyloid A (AA) amyloidosis. Recently, we have shown that murine SAA2.2, a non-amyloidogenic isoform in vivo, forms a hexamer in vitro containing a putative central channel. It is reported herein that upon thermal denaturation, hexameric SAA2.2 irreversibly dissociates to a misfolded monomer at physiological temperature, formation of which coincides with a significant loss of alpha-helical and gain of beta-sheet structure. When SAA2.2 is incubated for several days at 37 degrees C, sedimentation analytical ultracentrifugation reveals the presence of soluble high molecular weight aggregates, which upon further incubation undergo subsequent self-assembly into amyloid fibrils. Limited proteolysis experiments suggest that the in vitro amyloidogenecity of SAA2.2 is related to ...
Amyloid beta protein has been linked to the formation of Alzheimers disease in patients.¹ Plaques form from amyloid beta fibrils. The formation of these plaques between neural connections in the brain are associated with Alzheimers disease.² The reduction of the formation of fibrils can be linked to utilizing protein mimics. The protocols that are used to reproduce the simulation of amyloid beta in the brain can be very important. Also, the structure of the protein mimic that is being used to inhibit the formation of fibrils can determine how the amyloid beta plaques are reduced.
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 ...
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 ...
The precise cause of amyloid purpura is unknown, but several mechanisms are thought to contribute.[2] One may be a decrease in the level of circulating factor X,[2] a clotting factor necessary for coagulation. The proposed mechanism for this decrease in factor X is that circulating amyloid fibrils bind and inactivate factor X.[2] Another contributing factor may be enhanced fibrinolysis,[2] the breakdown of clots. Subendothelial deposits of amyloid may weaken blood vessels and lead to the extravasation of blood.[2][3] Amyloid deposits in the gastrointestinal tract and liver may also play a role in the development of amyloid purpura.[2] ...
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.
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 ...
(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 ...
This is a beautiful paper that follows a large body of excellent work from these investigators. However, no data is presented as to how the disruption of the interaction between SAP and amyloid fibrils by their drug candidate affects the fate of the amyloid itself. This paper is focused exclusively on the clearance of SAP from the deposits. The authors state that they hope that the clearance of SAP will reduce the stability of amyloid deposits and promote their regression. This is certainly a reasonable hypothesis, given that other studies have shown amyloid deposits can be cleared and that the SAP knockout mouse showed retarded and reduced disease.. However, it is very important to note that the systemic amyloidoses discussed in this paper seem to be caused by the amyloid fibrils themselves, whereas the neurodegenerative amyloidoses, including PD and AD, seem to be caused by a fibril precursor, or protofibril. In the latter cases, a molecule that promotes fibril accumulation (and protofibril ...
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
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 ...
Aortic medial amyloid (AMA) occurs as localised non-atheromatous plaques in virtually all individuals over the age of 50. The major protein component of AMA is the 50-residue polypeptide medin. Here we propose two methods of manipulating medin aggregation to reduce the cytotoxic species of medin: either by promoting formation of larger benign species or retaining small non-cytotoxic species. Medin co-localises with a variety of factors including glycosaminoglycans (GAGs). The first approach shows that the GAG heparin enhances the rate of medin aggregation and alters the morphology of the amyloid fibrils. Cellular viability measurements suggest that heparin eliminates small cytotoxic species of medin, promoting formation of benign fibrils. The second approach applies a previously successful approach of designing small peptide moieties that are complementary to the key amyloidogenic sequence but which contain modified amino acids known to disrupt hydrogen bonding and therefore prevent aggregation ...
Neurofibrillary tangles (NFTs) are one of the two hallmark lesions of Alzheimers disease (AD) and their accumulation has been used to assess the severity of the disease. They are composed of paired helical filaments (PHF), a form of amyloid resulting from the aggregation of the microtubule-associated protein tau. Our laboratory has found that peptides as short as 3-6 amino acids are able to initiate the formation of twisted filaments, similar to PHF. We believe that these short amyloid-forming peptides provide an excellent model for studying the structural basis of PHF and amyloid, in general. By understanding the structural basis for amyloid formation, a rational design of therapeutic agents able to prevent PHF accumulation can be undertaken. In addition to using short tau-related peptides to understand the basis of amyloid formation, they may be used as targeting agents for amyloid. For example, we have recently shown that contrast agents prepared from these peptides and a gadolinium chelate ...
2Institute for Medical Physics and Biophysics, University Leipzig, Germany. Amyloids are well ordered protein aggregates involved in many functional and pathogenic processes of life. Various structural models of the molecular architecture of amyloids have been derived in the last decade mainly driven by advances in solid state NMR. This talk will summarize our NMR efforts to study not only structural features of mature fibrils but the amyloid formation mechanism. Two systems will be covered: the Alzheimer peptide Aβ(1-40) and variants as well as the human parathyroid hormone PTH(1-84). For Aβ(1-40) we show that backbone hydrogen bonds are the main driving force for fibril structure formation overwriting side chain effect and buffer conditions [1,2]. Additionally, we show that morphological properties of fibril seeds do not necessarily propagate towards the growing fibril [3]. Several molecular observations during the formation of PTH(1-84) fibrils will be presented [4] to classify them as ...
2Institute for Medical Physics and Biophysics, University Leipzig, Germany. Amyloids are well ordered protein aggregates involved in many functional and pathogenic processes of life. Various structural models of the molecular architecture of amyloids have been derived in the last decade mainly driven by advances in solid state NMR. This talk will summarize our NMR efforts to study not only structural features of mature fibrils but the amyloid formation mechanism. Two systems will be covered: the Alzheimer peptide Aβ(1-40) and variants as well as the human parathyroid hormone PTH(1-84). For Aβ(1-40) we show that backbone hydrogen bonds are the main driving force for fibril structure formation overwriting side chain effect and buffer conditions [1,2]. Additionally, we show that morphological properties of fibril seeds do not necessarily propagate towards the growing fibril [3]. Several molecular observations during the formation of PTH(1-84) fibrils will be presented [4] to classify them as ...
This report represents the initial findings from what is designed to be a longitudinal study to delineate the natural history of amyloid deposition in eoFAD. To our knowledge, this is the first report of amyloid imaging in asymptomatic carriers of PS1 mutations, some of whom are more than 10 years younger than the age at which onset of cognitive symptoms would be expected (e.g., 48 years for the PS1C410Y mutation carriers). The findings suggest that amyloid deposition in these two families begins in the striatum well before the onset of cognitive symptoms.. Previous studies using structural MRI and [18F]fluorodeoxyglucose (FDG) PET determination of cerebral metabolic rate for glucose have shown changes in presymptomatic and symptomatic eoFAD subjects. Fox and colleagues (Schott et al., 2003; Ridha et al., 2006) reported that changes in hippocampal atrophy rate were evident 5.5 years before a diagnosis of AD. Two early reports showed decreased cerebral metabolism by FDG-PET in symptomatic eoFAD ...
The growth of amyloid fibrils requires a disordered or partially unfolded protein to bind to the fibril and adapt the same conformation and alignment established by the fibril template. Since the H-bonds stabilizing the fibril are interchangeable, it is inevitable that H-bonds form between incorrect pairs of amino acids which are either incorporated into the fibril as defects or must be broken before the correct alignment can be found. This process is modeled by mapping the formation and breakage of H-bonds to a one-dimensional random walk. The resulting microscopic model of fibril growth is governed by two timescales: the diffusion time of the monomeric proteins, and the time required for incorrectly bound proteins to unbind from the fibril. The theory predicts that the Arrhenius behavior observed in experiments is due to off-pathway states rather than an on-pathway transition state. The predicted growth rates are in qualitative agreement with experiments on insulin fibril growth rates as a ...
The cholesteryl-ester transfer protein (CETP) facilitates the transfer of cholesterol esters and triglycerides between lipoproteins in plasma where the critical site for its function is situated in the C-terminal domain. Our group has previously shown that this domain presents conformational changes in a non-lipid environment when the mutation D470N is introduced. Using a series of peptides derived from this C-terminal domain, the present study shows that these changes favor the induction of a secondary β-structure as characterized by spectroscopic analysis and fluorescence techniques. From this type of secondary structure, the formation of peptide aggregates and fibrillar structures with amyloid characteristics induced cytotoxicity in microglial cells in culture. These supramolecular structures promote cell cytotoxicity through the formation of reactive oxygen species (ROS) and change the balance of a series of proteins that control the process of endocytosis, similar to that observed when β-amyloid
α2-Macroglobulin (α2M) is an extracellular chaperone that inhibits amorphous and fibrillar protein aggregation. The reaction of α2M with proteases results in an activated conformation, where the proteases become covalently-linked within the interior of a cage-like structure formed by α2M. This study investigates, the effect of activation on the ability of α2M to inhibit amyloid formation by Aβ1-42 and I59T human lysozyme and shows that protease-activated α2M can act via two distinct mechanisms: (i) by trapping proteases that remain able to degrade polypeptide chains and (ii) by a chaperone action that prevents misfolded clients from continuing along the amyloid forming pathway.
After dealing with disease or defect for a long period of time, the body may start to produce abnormally folded protein deposits. This process is referred to as amyloidosis, and the deposits themselves have been termed
Amyloidosis is a condition in which a waxy translucent substance - consisting primarily of protein - deposits in a cats organs and tissues. Prolonged excess of this condition may lead to organ failure.
The spectral count analysis of diseased and control tissues did not indicate accumulation of any TGFBIp polypeptide region in either GCD1 or LCD1 when compared with control tissue (Fig. 2). Korvatska et al.,32 reported altered processing of TGFBIp in R124C corneal tissue leading to accumulation of the N-terminal part of TGFBIp within the stroma. In addition, Schmitt-Bernard and colleagues33 showed that a polypeptide region within the first FAS1 domain of TGFBIp had a high propensity for amyloid fibrillation in vitro. Both stromal and Bowmans deposits are most abundantly represented by the semitryptic peptides within the polypeptide region L128-R172 constituting approximately 30% of all semitryptic peptides observed for both types of amyloid deposits. In addition a significant increase in abundance of this L128-R172 region by approximately 50% in the stromal amyloid deposits compared to the same polypeptide region in the control group was observed (Fig. 2B). The polypeptide region L128-R172 ...
The aggregation of peptides and proteins into highly organized aggregates such as amyloid fibrils is a very important and fundamental process in biology. Most p...
Misfolding of proteins and peptides is closely linked to several neurodegenerative disorders, among them Alzheimers disease (AD), the most prominent example of brain diseases. The self-assembly of the amyloid β peptide (Aβ) into amyloid fibrils is one histologic hallmark of AD. A detailed knowledge about the underlying mechanism(s) of Aβ aggregation is crucial for advances toward a fundamental understanding of the disease, which may promote the search for and design of efficient therapeutics. The work presented in this thesis deals with modulation of the aggregation process by various compounds, i.e. small organic molecules (e.g. lacmoid and Congo red), surfactants and metal ions. These results provide insight into the molecular mechanism of modulator interactions and interference with Aβ and its aggregation pathways. Applying a combination of kinetic and dynamic studies as well as structural investigations we characterized the molecular interactions between Aβ and aggregation modulators ...
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 ...
Ver más] α-Synuclein (αSyn) is a 140-residue amyloid-forming protein whose aggregation is linked to Parkinsons disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective αSyn-based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat-shock proteins (HSPs): their classical "chaperone" activities and their recently discovered and diverse "immunoactive" properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an αSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the αSyn/Hsp70 complex, including a restrained αSyn-specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4+CD25+Foxp3+) and Teff (CD4+Foxp3−) cell populations, as opposed to significant changes in ...
Peptides , Amyloid Peptides , Beta-Amyloid Peptide Fragments , Beta-Amyloid (16-22), Human, mouse/rat; This is a short fragment of the b-Amyloid peptide containing two aromatic phenylalanine residues. Short peptide models have provided novel insight into the mechanistic issues of amyloid formation. This heptapeptide fragment has the capacity of forming typical amyloid fibrils in vitro. Aromatic interactions are important in many cases of amyloid formation.; KLVFFAE; H-Lys-Leu-Val-Phe-Phe-Ala-Glu-OH
Abstract: The principal constituent of amyloid plaques found in the brains of individuals with Alzheimers disease (AD) is a 39-42-amino-acid protein, amyloid β protein (Aβ). This study examined whether the measurement of Aβ levels in CSF has diagnostic value. There were 108 subjects enrolled in this prospective study: AD (n = 39), non-AD controls (dementing diseases/syndromes; n = 20), and other (n = 49). CSF was obtained by lumbar puncture, and Aβ concentrations were determined using a dual monoclonal antibody immunoradiometric sandwich assay. The mean Aβ value for the AD group (15.9 ± 6.8 ng/ml) was not significantly different from that for the non-AD control group (13.0 ± 7.1 ng/ml; p = 0.07), and substantial overlap in results were observed. Aβ values did not correlate with age (r = −0.05, p = 0.59), severity of cognitive impairment (r = 0.22, p = 0.21), or duration of AD symptoms (r = 0.14, p = 0.45). These findings are in conflict with other reports in the literature; discrepant ...
In many cases of protein aggregate formation, a key component is the interaction of amyloid proteins and cellular surfaces, especially lipid bilayer membranes. Bilayer-protein interactions have been shown in this paper to modulate protein misfolding and play a somewhat catalytic role in protein aggregate propagation. Furthermore, in cases such as the common AB amyloid-forming proteins as well as IAPP and htt, the binding to lipid bilayers can cause conformational changes in the permeability and stability of the membrane, leading to cell death. Furthermore, some bilayer-amyloid interactions can stabilize the aggregate form of the protein and promote propagation of the aggregation process. These interactions occur through transmembrane domains present in AB or chemical reactions that alter permeability and surface tension of the membranes. These cases allow us to understand the importance of direct cell membrane interactions with aggregate-forming proteins and the need to detect/identify specific ...
Kundu, B., Maiti, N. R., Jones, E. M., Surewicz, K. A., Vanik, D. L., Surewicz, W. K., Nucleation-dependent conformational conversion of the Y145Stop variant of human prion protein: Structural clues for prion propagation. Proc. Natl. Acad. Sci. U.S.A. 100, 12069-12074 (2003 ...
In 1984, Beyreuther and Masters purified and sequenced the amyloid constituent of the plaque in Alzheimers disease, and three years later, their group used this sequence to clone the gene encoding the Aβ amyloid peptide located on chromosome 21. These studies demonstrated that the Aβ amyloid was derived by proteolytic cleavage of a neuronal transmembrane receptor. Subsequent studies by many groups has shown that a variety of Aβ-amyloid oligomers lie at the centre of AD pathogenesis, and these are now the validated primary targets for both diagnostic and therapeutic strategies. Masters and Beyreuther therefore defined the principal molecular and genetic pathways leading to the current Aβ amyloid theory of causation of Alzheimers disease ...
There is provided a series of novel α-(N-sulfonamido)acetamide compounds of the Formula (I) wherein R, R1, R2 and R3 are defined herein, which are inhibitors of β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimers Disease and other conditions affected by anti-amyloid ac ...
Beta- amyloid peptide ( Aβ) is the major protein constituent found in senile plaques in Alzheimers disease ( AD). Aβ is able to bind in the cell membrane to a variety of biomolecules, including lipids and protein, but the sequence of biological events that leads to cell death is not well understood. Its extracellular accumulation is believed to be related with neurodegeneration and its toxicity related to its structure or aggregation state. The purpose of this study was to characterize Aβ structure; first, at the residue level to identify which residues have an important role on peptides tertiary structure, followed by the examination of its interactions with the cell membrane, with residue level resolution. An approach based on chemical modification of primary amines and mass spectrometric ( MS) detection was used to identify residues on Aβ peptide that were exposed or buried upon changes in peptide structure associated with aggregation. Tandem mass spectrometry and limited proteolysis ...
Protein aggregation is common to dozens of diseases including prionoses, diabetes, Parkinsons and Alzheimers. Over the past 15 years, there has been a paradigm shift in understanding the structural
The subject of this research project is to develop and experimentally validate a novel computational approach to analyze structural ensembles in proteins and pe...
A new protein which will help scientists to understand why nerve cells die in people with Alzheimers disease has been designed in a University of Sussex laboratory. In people with Alzheimers, Amyloid-beta (Abeta) proteins stick together to make amyloid fibers which form clumps between neurons in the brain. It is believed the build-up of these clumps causes brain cells to die, leading to the cognitive decline in patients suffering from the disease. Now, the University of Sussex scientists have created a new protein which closely resembles the Abeta protein in size and shape but contains two different amino acids (the building blocks that proteins are made up of). These changes mean that the new protein does not form amyloid fibres or sticky clumps and, unlike Abeta, is not toxic to nerve cells. To read more, click here.. ...
beta Amyloid (1-40) antibody [4H308] (amyloid beta (A4) precursor protein) for IHC-P, WB. Anti-beta Amyloid (1-40) mAb (GTX17420) is tested in Human, Mouse samples. 100% Ab-Assurance.
How is New Amyloid Component Protein abbreviated? NACP stands for New Amyloid Component Protein. NACP is defined as New Amyloid Component Protein very rarely.
Amyloid fibrils play a role in a number of neuro-degenerative diseases such as Alzheimers and Parkinsons, as well as Type 2 diabetes. They are tiny and t
de Souto Barreto P, Vellas B, Andrieu S, Rolland Y. J Prev Alz Dis 2015;2:56-63. Publication date: March 1, 2015. Summary. Physical activity (PA) contributes to brain health and plasticity, which suggests that PA would protect against the development of Alzheimers disease (AD). However, research on PA and AD biomarkers is very scarce.. The objective of the present study was to perform a systematic review of studies that investigated the associations between PA and β-amyloid brain deposition in humans. Electronic searches were performed in PubMed, Cochrane Library, SportDiscus, PEDro, and PsychInfo databases. Articles were eligible if they have assessed both PA and β-amyloid brain deposition in humans.. Five articles, published between 2010 and 2013, met eligibility criteria (study population varied across studies from 54 to 515, according with the β-amyloid measure. All five studies assessed both PA and PET-amyloid; among them, two studies also assessed CSF Aβ42 levels). All studies were ...
Does aluminium bind to histidine An NMR investigation of amyloid 12 and amyloid 16 fragments Chemical Biology and Drug Design , 2013, 82 , 48-59 Priya Narayan, Bankala Krishnarjuna, Vinaya Vishwanathan, Dasappa Jagadeesh Kumar, Sudhir Babu, Krishna Venkatachala Ramanathan, Kalpathy Ramaier Katchap Easwaran, Holenarasipur GunduRao Nagendra,...
A method for the synthesis and high purification of fragments of Aβ(1-42) peptide has been elaborated. We have synthesized the amyloidogenic fragment Aβ(16-25) predicted by us and studied the process of its aggregation by electron microscopy and X-ray analysis. Electron microscopy images show that the peptide forms a film, which is not characteristic of amyloid fibrils. At the same time, according to the X-ray diffraction data, its preparations display the presence of two main reflections (4.6-4.8 and 8-12 Å) characteristic of cross-β structure of amyloid fibrils. Thus, the fragment Aβ(16-25) that we predicted is a promising object not only for studying the process of polymerization of the peptides/proteins, but also for using it as a nanomaterial to study a number of biological processes ...
PhD Project - Inhibiting protein-protein interactions in the early stages of amyloid formation at University of Leeds, listed on FindAPhD.com
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Page contains details about amyloid fibers . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com
The present invention provides an in vitro tissue culture-based assay for amyloid deposition specific for Alzheimers disease which is suitable for routine drug screening analysis. Immunological diagnostic reagents for Alzheimers disease are also provided.
This syndrome is difficult to treat and has a guarded to poor prognosis. Most animals will have episodes of fever and cholestasis, where bile cannot flow from the liver to the duodenum (small intestine). Some cats will benefit from medication, with resolved clinical signs and diminished hepatic amyloid. However, cats surviving liver hemorrhage eventually succumb to renal failure. Your veterinarian will schedule follow-up appointments with you for your cat as is necessary to monitor its organ function.. ...
Jülich / Düsseldorf / Hamburg / Maastricht, 7 September 2017 - A team of researchers from Germany and the Netherlands have determined the structure of an amyloid fibril with previously unachieved resolution. The fibrils of the bodys own amyloid beta (Aβ) protein are the main constituent of Alzheimers disease related and characteristic pathological protein deposits in the brain. The atomic-level three-dimensional structure elucidated by scientists from Forschungszentrum Jülich, Heinrich Heine University Düsseldorf, the Centre for Structural Systems Biology in Hamburg, and Maastricht University displays previously unknown structural details which can answer many questions on the growth of harmful deposits and also explain the effect of genetic risk factors. The results have been published in the renowned journal Science.
Ong, W.Y.,He, Y.,Garey, L.J. (1997). Distribution of Amyloid β-protein Immunoreactivity in the Hippocampus of Rats Injected with Kainate. Journal of Brain Research 38 (3) : 353-361. [email protected] Repository ...
Bachem offers H-1388 Amyloid β-Protein (10-20) for your research. Find all specific details here. Find product specific information including available pack sizes, CAS, detailed description and references here.
Abcams Amyloid beta 1-40 ELISA Kit suitable for Cell culture supernatant, Serum, Plasma in human. Reliably quantify 0.1 ng/ml of Amyloid beta 1-40.
What level of KD needed for clinical benefit? Based on other amyloid diseases and liver transplant data: as little as 50% over time is sufficient for regression of amyloid deposition. Would hope to get doses giving 50-80% KD to advance into pivotal studies. Hope to achieve with TTR01, and certainly think it is achievable in TTR02 backup program with next generation LNPs ...
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With few approved drugs available to treat Alzheimer disease, researchers are working on new compounds that block amyloid formation. But many potential drugs in the pipeline for the disease and other amyloid-associated illnesses may not be as promising as thought, according to a new linkurl:study;http://www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.65.html published today (January 27) in Nature Chemical Biology. The research, led by linkurl:Brian Shoichet;http://ucsf.edu/dbps/facu
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The efficacy of the IgG1κ c11-1F4 mAb to accelerate amyloidolysis in our in vivo amyloidoma model was compared with that of the murine parent. Because the 22C1-, 22C5-, and 22D2-derived c11-1F4 preparations exhibited equivalent reactivity with amyloid and there were limited quantities of each, the three were combined and used in our in vivo experiments. Given the relatively large amount of amyloid extract required to produce a readily palpable amyloidoma (dry weight, 100 mg) and the scarcity of autopsy-derived samples, the numbers of animals used in each study was necessarily restricted to one pair of mice. In the first experiment, four sets were injected s.c. with a 1-ml volume of solution containing 100 mg of a human ALκ extract (Ref. 19 ; patient HIG) that was comprised of fragments (∼16 and 18 kDa) representing the major portion of the amyloidogenic precursor κ1 light chain (BJP, HIG), as demonstrated by SDS-PAGE, Western blot, and chemical analyses. By dot blot, the c11-1F4 mAb, as ...
The phospholipase D3 (PLD3 ) gene has shown association with Alzheimers disease (AD). However, the role of PLD3 common variants in amyloid-β (Aβ ) pathology remains unclear. We examined the association of thirteen common single nucleotide polymorphi
JPT Peptide Technologies is a DIN ISO 9001:2015 certified and GCLP compliant integrated provider of innovative peptide based catalog products and custom services.
Amyloid ß25-35 (Aß25-35) represents a neurotoxic fragment of Aß1-40 or Aß1-42, and is implicated in the progressive neurodegeneration in cases of the Alzheimer disease (AD). Amyloid ß25-35 was shown to lyse rat erythrocytes (RBCs) of all ages, and the extent of the RBC toxicity is directly correlated with Aß25-35 concentration and cell age. Activities of glycolytic, antioxidant, and Na+/K+-adenosine triphosphatase (ATPase) enzymes, in vivo, are significantly decreased in older RBCs as compared to the young RBCs. In vitro, Aß25-35 reduced activities of hexokinase, phosphofructokinase, pyruvate kinase, glutathione peroxidase, and glutathione transferase and increased Na+/K+-ATPase activity; these effects are significantly greater in aged RBCs as compared to those of the younger cells. The diminution in activity of certain enzymes may determine the life span of the RBCs in vivo and may be relevant to the human AD; higher sensitivity of older RBCs to Aß25-35 toxicity may contribute to the ultimate
(Medical Xpress) -- Researchers from the University of California have found that a peptide that forms deposits in the human brain and is thought to be responsible for the onset of Alzheimer’s disease, behaves in ways ...
Commander beta Amyloid anticorps monoclonal et polyclonal pour beaucoup dapplications. Selection de fournisseur de qualité pour anti-beta Amyloid anticorps.
Aberrant protein folding and self-assembly underlie over 30 human diseases called amyloidoses, for which currently there is no cure. The diseases range from tissue-specific to systemic and from geneti
Abcam provides specific protocols for Anti-Amyloid Precursor Protein antibody (ab2073) : Immunohistochemistry protocols, Immunocytochemistry &…
The immune systems response against amyloid-beta the protein that fo... Our results provide in vivo evidence that the brains immune system p...While it has been known that the immune system reacts against amyloid-...The research team focused on a molecule called CCR2 a receptor on the...,Blocking,immune,cell,action,increases,Alzheimers-associated,protein,deposits,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
Ac-Beta-Amyloid-Protein (15-20) amide, 1 mg. Incubation of Ac-QKLVFF-NH2 with the amyloid ��-protein (1-40) inhibited polymerization of the amyloid ��-protein (1-40) into amyloid fibrils.
Synthetic peptide that forms fibrils with have the same antigenic and structural features as those of native AD amyloid filaments.
Evidence from clinical studies (Wang et al., 1999; Naslund et al., 2000), in vitro experiments (Lambert et al., 1998; Hartley et al., 1999; Chromy et al., 2003), and in vivo experiments (Shin et al., 1997; Hsia et al., 1999) suggest that the initial pathogenesis of AD is due to the build up of neurotoxic aggregates of the soluble Aβ peptide species Aβ(1-40) and Aβ(1-42). As a result, a number of therapeutic approaches for lowering amyloid are in progress, one of which is the use of γ-secretase inhibitors (Hardy and Selkoe, 2002; Harrison et al., 2004b). With the advent of orally available γ-secretase inhibitors, studies in transgenic mice using these inhibitors have demonstrated reductions of Aβ levels in the brain, CSF, and plasma (Dovey et al., 2001; Lanz et al., 2003, 2004; Wong et al., 2004). However, these models have high levels of Aβ not representative of normal physiological rodent levels.. A previous study used immunoprecipitation and Western blotting to determine the effect of ...
Solanezumab, a monoclonal antibody-based treatment for Alzheimers disease developed by Eli Lilly that targets amyloid plaques, did not ...
A team of researchers at Weill Cornell Medical College has discovered that amyloid peptides are harmful to the blood vessels that supply the brain with blood in Alzheimers disease-thus accelerating cognitive decline by ...
Recombinant Human beta Amyloid 1-42 protein Full length protein datasheet (ab82795). Abcam offers quality products including antibodies, assays and other…
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
The 37-residue human islet amyloid polypeptide (hIAPP or amylin) self-assembles into fibers, the assembly of which has been associated with the disease mechanism of type II diabetes. Infrared spectroscopy in conjunction with isotope labeling is proving to be a powerful tool for studying the aggregation process of hIAPP and other amyloid forming proteins with residue specific structure and kinetic information, but the relationship between the spectroscopic observables and the structure is not fully established. We report a detailed analysis of the linear and 2D IR spectra of hIAPP fibers isotope labeled at seven different residue positions. The features of the 2D IR spectra, including the frequencies, linewidths, intensities, and polarization dependence of the diagonal and cross-peaks, rely heavily on the position of the isotope labeled residue. In order to understand how these measured parameters depend on fiber secondary and tertiary structure, we have simulated 1D and 2D IR spectra utilizing ...
Looking for online definition of amyloid light chain protein in the Medical Dictionary? amyloid light chain protein explanation free. What is amyloid light chain protein? Meaning of amyloid light chain protein medical term. What does amyloid light chain protein mean?
The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of TTR causes life-threatening transthyretin amyloidosis (ATTR) associated with three conditions traditionally known as senile systemic amyloidosis, familial amyloidotic polyneuropathy, and familial amyloidotic cardiomyopathy. Senile systemic amyloidosis is a late onset disease in which Tafamidis, a TTR tetramer stabilizer, has been recently approved in Europe; it delays progression of the disease. Several other therapeutics are currently in clinical trials, including other tetramer stabilizers such as diflunisal and RNAi therapies that cause a decrease in the production of TTR protein. Additional approaches are needed to prevent ATTR, and here we explore the use of peptide inhibitors that block aggregation of TTR. Several models of the TTR amyloid spine have been proposed, but the aggregation-prone segments of the protein remain uncertain. Based on the ...
Looking for online definition of German-type amyloid neuropathy in the Medical Dictionary? German-type amyloid neuropathy explanation free. What is German-type amyloid neuropathy? Meaning of German-type amyloid neuropathy medical term. What does German-type amyloid neuropathy mean?
Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014. Summary. Global Markets Direct s, Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014, provides an overview of the indication s therapeutic pipeline. This report provides information on the therapeutic development for Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease), complete with latest updates, and special features on late-stage and discontinued projects. It also reviews key players involved in the therapeutic development for Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease). Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, Half Year is built using data and information sourced from Global Markets Direct s proprietary databases, Company/University websites, SEC filings, investor ...
Transthyretin (TTR) is a homotetrameric serum protein associated with amyloidoses such as familial amyloid polyneuropathy and senile systemic amyloidosis. The amyloid fibril formation of TTR can be inhibited through stabilization of the TTR tetramer by the binding of small molecules. In this study, we examined the inhibitory potency of caffeic acid phenethyl ester (CAPE) and its derivatives. Thioflavin T assay showed that CAPE suppressed the amyloid fibril formation of TTR. Comparative analysis of the inhibitory potencies revealed that phenethyl ferulate was the most potent among the CAPE derivatives. The binding of phenethyl ferulate and the selected compounds to TTR were confirmed by the 8-anilino-1-naphthalenesulfonic acid displacement and X-ray crystallography. It was also demonstrated that Bio 30, which is a CAPE-rich commercially available New Zealand propolis, inhibited ...
TY - JOUR. T1 - Immunoglobulin light chain amyloidosis is diagnosed late in patients with preexisting plasma cell dyscrasias. AU - Kourelis, Taxiarchis. AU - Kumar, Shaji K. AU - Go, Ronald S.. AU - Kapoor, Prashant. AU - Kyle, Robert A.. AU - Buadi, Francis K.. AU - Gertz, Morie. AU - Lacy, Martha. AU - Hayman, Suzanne R.. AU - Leung, Nelson. AU - Dingli, David M. AU - Lust, John A.. AU - Lin, Yi. AU - Zeldenrust, Stephen R.. AU - Rajkumar, S Vincent. AU - Dispenzieri, Angela. PY - 2014/11/1. Y1 - 2014/11/1. N2 - AL amyloidosis (AL) is rare and frequently remains undiagnosed until organ function is compromised, even among patients with known pre-existing untreated plasma cell dyscrasias (PCD). We identified 168 patients with AL amyloidosis who had a prior untreated PCD. The earliest symptom or sign (s/s) was defined as the first symptom reported by the patient that could be attributed to organ dysfunction caused by AL. The interval from the time of development of s/s to the establishment of ...
TY - JOUR. T1 - Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity. AU - Solesio, María E.. AU - Peixoto, Pablo M.. AU - Debure, Ludovic. AU - Madamba, Stephen M.. AU - de Leon, Mony J.. AU - Wisniewski, Thomas. AU - Pavlov, Evgeny. AU - Fossati, Silvia. PY - 2018/8/1. Y1 - 2018/8/1. N2 - Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimers disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was effective at ...

Hereditary cerebral amyloid angiopathy Dutch type symptoms, treatments & forums | PatientsLikeMeHereditary cerebral amyloid angiopathy Dutch type symptoms, treatments & forums | PatientsLikeMe

See how people just like you are living with hereditary cerebral amyloid angiopathy Dutch type. Learn from their data and ... What is hereditary cerebral amyloid angiopathy Dutch type?. Hereditary cerebral amyloid angiopathy is characterized as a ... Hereditary cerebral amyloid angiopathy Dutch type Were all in this for good.. ... Amyloid proteins build up in the arteries of the brain, which leads to an increased risk of dementia and stroke. ...
more infohttps://www.patientslikeme.com/conditions/hereditary-cerebral-amyloid-angiopathy-dutch-type

Islet amyloid polypeptide, islet amyloid, and diabetes mellitusIslet amyloid polypeptide, islet amyloid, and diabetes mellitus

... Westermark, Per Uppsala University, Disciplinary Domain of ... Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of beta-cells of the pancreatic islets of ... IAPP was discovered through its ability to aggregate into pancreatic islet amyloid deposits, which are seen particularly in ... including mechanisms whereby human IAPP forms toxic aggregates and amyloid fibrils. ...
more infohttp://uu.diva-portal.org/smash/record.jsf?pid=diva2:433916

Computational Modelling of the Human Islet Amyloid Polypeptide | Ebook | Ellibs EbookstoreComputational Modelling of the Human Islet Amyloid Polypeptide | Ebook | Ellibs Ebookstore

Computational Modelling of the Human Islet Amyloid Polypeptide - Author: Skeby, Katrine Kirkeby - Price: 138,35€ ... 1. Amyloid and Amyloid Fibrils. Katrine Kirkeby Skeby. 2. Computational Theory. Katrine Kirkeby Skeby. 3. Imaging Agent Binding ... Computational Modelling of the Human Islet Amyloid Polypeptide. 138,35€. Add to cart. Ebook, PDF with Adobe DRM. ISBN: ... 6. Coarse Grained Study of Amyloid Protofibril Aggregation. Katrine Kirkeby Skeby. 7. Conclusion and Perspectives. Katrine ...
more infohttps://www.ellibs.com/book/9783319200408/computational-modelling-of-the-human-islet-amyloid-polypeptide

Cerebral amyloid angiopathy related lobar hemorrhage | Radiology Case | Radiopaedia.orgCerebral amyloid angiopathy related lobar hemorrhage | Radiology Case | Radiopaedia.org

The Boston criteria for probable cerebral amyloid angiopathy are: appropriate clinical history Age ≥55 years MR imaging: ... Cerebral amyloid angiopathy related lobar hemorrhage. Case contributed by Dr Hidayatullah Hamidi ... noted probably due to microangiopathic changes secondary to amyloid-ß peptide deposition in the arterial walls. ...
more infohttps://radiopaedia.org/cases/cerebral-amyloid-angiopathy-related-lobar-haemorrhage

Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino De Andrades Disease) - Pipeline Review, H1 2014 | Feb 14,...Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino De Andrade's Disease) - Pipeline Review, H1 2014 | Feb 14,...

Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014 ... provider of premium market research reports announces the addition of Familial Amyloid Polyneuropathy (Transthyretin ... Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014. Summary. ... Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino De Andrades Disease) - Pipeline Review, H1 2014. ...
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Cerebral Amyloid Angiopathy in the Aetiology of Alzheimers disease and its effect on Therapy.  - ePrints SotonCerebral Amyloid Angiopathy in the Aetiology of Alzheimer's disease and its effect on Therapy. - ePrints Soton

Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older ... Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older ... Carare, Roxana-Octavia, Preston, S.D., Subash, M. and Weller, R.O. (2009) Cerebral Amyloid Angiopathy in the Aetiology of ... Cerebral Amyloid Angiopathy in the Aetiology of Alzheimers disease and its effect on Therapy. ...
more infohttps://eprints.soton.ac.uk/142285/

Get PDF - IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic miceGet PDF - IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice

IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice ... The ability of rodent islet amyloid polypeptide to inhibit amyloid formation by human islet amyloid polypeptide has important ... Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/ ... Islet amyloid-associated diabetes in obese A(vy)/a mice expressing human islet amyloid polypeptide. Diabetes 47(5): 743-750, ...
more infohttps://eurekamag.com/research/058/030/058030578.php

Cerebral -amyloid detected by Pittsburgh compound B positron emission topography predisposes
      to recombinant tissue...Cerebral -amyloid detected by Pittsburgh compound B positron emission topography predisposes to recombinant tissue...

Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 2007;62:229-234. 3. Ly JV, Donnan GA, ... Cerebral amyloid angiopathy without and with cerebral hemorrhages A comparative histological study. pdf1 187 Кб ... Imaging beta-amyloid burden in aging and dementia. Neurology 2007;68:1718-1725. Nothing to report. References 1. McCarron MO, ... Cerebral amyloid angiopathy pathology and cognitive domains in older persons. pdf156 Кб ...
more infohttps://www.docme.ru/doc/1914512/cerebral--amyloid-detected-by-pittsburgh-compound-b-posit..

What factors predict bleeding from cerebral amyloid angiopathy? - Neurochecklists BlogWhat factors predict bleeding from cerebral amyloid angiopathy? - Neurochecklists Blog

Abstract BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy ... The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid ... Categories VasculopathyTags CAA, cerebral amyloid angiopathy, intracerebral haemorrhage, Lancet Neurol, Lerpiniere C, Rodrigues ... What factors predict bleeding from cerebral amyloid angiopathy?. The Edinburgh CT and genetic diagnostic criteria for lobar ...
more infohttps://neurochecklistsupdates.wordpress.com/2018/12/16/what-factors-predict-bleeding-from-cerebral-amyloid-angiopathy/

Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic StrokeLateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke

Inflammatory Cerebral Amyloid Angiopathy, Amyloid-β-Related Angiitis, and Primary Angiitis of the Central Nervous System: ... Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke Yi Li*, Ayman Al-Salaimeh, Elizabeth ... Cerebral amyloid angiopathy (CAA) is characterized by the deposition of fibrillar protein with beta-pleated sheet configuration ... How to cite this article: Li Y, Al-Salaimeh A, DeGrush E, Moonis M. Lateralized Cerebral Amyloid Angiopathy presenting with ...
more infohttps://www.heighpubs.org/jnnd/jnnd-aid1005.php

Familial amyloid polyneuropathy (FAP), in an inborn habitat of Hiroshima Prefecture, Japan<...Familial amyloid polyneuropathy (FAP), in an inborn habitat of Hiroshima Prefecture, Japan<...

Familial amyloid polyneuropathy (FAP), in an inborn habitat of Hiroshima Prefecture, Japan. / Nitta, K.; Kito, S.; Harada, T.; ... Familial amyloid polyneuropathy (FAP), in an inborn habitat of Hiroshima Prefecture, Japan. Clinical Neurology. 1986 9 1;26(9): ... Nitta, K. ; Kito, S. ; Harada, T. ; Sakaki, Y. ; Sasaki, H. / Familial amyloid polyneuropathy (FAP), in an inborn habitat of ... Nitta, K., Kito, S., Harada, T., Sakaki, Y., & Sasaki, H. (1986). Familial amyloid polyneuropathy (FAP), in an inborn habitat ...
more infohttps://kyushu-u.pure.elsevier.com/ja/publications/familial-amyloid-polyneuropathy-fap-in-an-inborn-habitat-of-hiros

Journal Club Review: Cerebral Amyloid Angiopathy with and without Haemorrhage | Neurology Online Journal ClubJournal Club Review: "Cerebral Amyloid Angiopathy with and without Haemorrhage | Neurology Online Journal Club

Amyloid deposition in small arteries of the cerebrum leads to friability and haemorrhage. There are also rare familial forms of ... Background Sporadic cerebral amyloid angiopathy (CAA) is the most common cause of lobar intracranial haemorrhage, which in ... one who have amyloid deposition in blood vessels as part of some other amyloid process, possibly a by-product of dementia- ... Journal Club Review: "Cerebral Amyloid Angiopathy with and without Haemorrhage. Posted on May 12, 2015 by dulcetware ...
more infohttps://neurologyonlinejournalclub.com/2015/05/12/journal-club-review-cerebral-amyloid-angiopathy-with-and-without-haemorrhage/

Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014- CFDMaster...Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrade's Disease) - Pipeline Review, H1 2014- CFDMaster...

Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014 31st ... Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline by SOM Biotech SL, H1 2014 ... Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline by Pfizer Inc., H1 2014 19 ... Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Products Glance 12. Late ...
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Strategies for Extracting Structural Information from 2D IR Spectroscopy of Amyloid: Application to Islet Amyloid Polypeptide |...Strategies for Extracting Structural Information from 2D IR Spectroscopy of Amyloid: Application to Islet Amyloid Polypeptide |...

Strategies for Extracting Structural Information from 2D IR Spectroscopy of Amyloid: Application to Islet Amyloid Polypeptide. ... Strategies for Extracting Structural Information from 2D IR Spectroscopy of Amyloid: Application to Islet Amyloid Polypeptide. ... The 37-residue human islet amyloid polypeptide (hIAPP or amylin) self-assembles into fibers, the assembly of which has been ... This latter approach is not limited to amyloid fibrils and will be generally useful in identifying regions of secondary ...
more infohttp://zanni.chem.wisc.edu/content/strategies-extracting-structural-information-2d-ir-spectroscopy-amyloid-application-islet

Alzheimers Brain Plaques - Alzheimers AssociationAlzheimer's Brain Plaques - Alzheimer's Association

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 ...
more infohttps://www.alz.org/braintour/plaques.asp

Amyloid | SpringerLinkAmyloid | SpringerLink

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 ...
more infohttps://link.springer.com/referenceworkentry/10.1007/978-1-60761-219-3_6

Amyloid Proteins | SpringerLinkAmyloid Proteins | SpringerLink

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 ...
more infohttps://link.springer.com/book/10.1007%2F978-1-4939-7816-8

Amyloid | Newsroom - McGill UniversityAmyloid | Newsroom - McGill University

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.... ...
more infohttps://mcgill.ca/newsroom/category/tags/amyloid

What is amyloid arthropathy?What is amyloid arthropathy?

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 ...
more infohttps://www.medscape.com/answers/335414-106026/what-is-amyloid-arthropathy

Amyloid Cascade HypothesisAmyloid Cascade Hypothesis

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 ...
more infohttps://www.news-medical.net/life-sciences/Amyloid-Cascade-Hypothesis.aspx

What is prolactin amyloid (Apro)?What is prolactin amyloid (Apro)?

... 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]. ...
more infohttps://www.medscape.com/answers/335414-106011/1102860-overview

amyloid | Weizmann Institute of Scienceamyloid | Weizmann Institute of Science

Weizmann Institute of Science234 Herzl Street, Rehovot 7610001 IsraelTel: +972-8-934-9106 Terms of UseDisclaimerAccessibilitySite MapWeizmann CareersContact Us. ...
more infohttp://www.weizmann.ac.il/pages/tags/amyloid

β-Amyloid (4G8) | ALZFORUMβ-Amyloid (4G8) | ALZFORUM

the epitope lies within amino acids 18-22 of beta amyloid (VFFAE) ... β-Amyloid (4G8). Quick Links. *Overview. *Comments / Questions ...
more infohttps://www.alzforum.org/antibodies/v-amyloid-4g8-0

Cerebral amyloid angiopathy: MedlinePlus Medical EncyclopediaCerebral amyloid angiopathy: MedlinePlus Medical Encyclopedia

... is a condition in which proteins called amyloid build up on the walls of the arteries in the brain. CAA increases the risk for ... Cerebral amyloid angiopathy (CAA) is a condition in which proteins called amyloid build up on the walls of the arteries in the ... Yamada M. Cerebral amyloid angiopathy: emerging concepts. J Stroke. 2015;17(1):17-30. PMID: 25692104 www.ncbi.nlm.nih.gov/ ... People with CAA have deposits of amyloid protein in the walls of blood vessels in the brain. The protein is usually not ...
more infohttps://medlineplus.gov/ency/article/000719.htm

Amyloid Cardiomyopathy | Boston Medical CenterAmyloid Cardiomyopathy | Boston Medical Center

BMC is an international referral center for the diagnosis and treatment of systemic amyloid diseases. BMC is one of the few ... studies examining the biochemical basis of amyloid toxicity, and projects examining the best treatment of patients with cardiac ... please contact the program office at 617.638.4317 or visit the Amyloid Center Webpage. ...
more infohttps://www.bmc.org/amyloid-cardiomyopathy
  • 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)
  • This entry represents the propeptide (Pro-islet amyloid polypeptide) prior to cleavage into islet amyloid polypeptide. (ebi.ac.uk)
  • The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or amylin. (wikipedia.org)
  • 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)
  • 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)
  • What is the amyloid cascade hypothesis? (news-medical.net)
  • The amyloid cascade hypothesis was initially suggested in 1992. (news-medical.net)
  • 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)
  • 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)
  • Greenberg SM, Charidimou A. Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. (medlineplus.gov)
  • In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. (hindawi.com)
  • Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. (hindawi.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)
  • 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)
  • 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)
  • 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)
  • 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)
  • CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. (ebi.ac.uk)
  • These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes inhomogeneous structures. (wikipedia.org)
  • 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)
  • We are working on building high-resolution predictions for medically relevant amyloids, starting with the Alzheimer\'s-beta fragment (1-40). (bakerlab.org)
  • Carpal tunnel syndrome can be the presenting sign of primary or secondary forms of amyloid, as only minimal deposits are required to impair nerve conduction. (medscape.com)
  • Amyloid arthropathy can mimic classic RA but usually lacks the intense distal synovitis and can affect the hips, knees, and shoulders more than peripheral joints. (medscape.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)
  • The classic "shoulder-pad" sign denotes end-stage amyloid deposits in the shoulder synovium and periarticular structures, but is rarely seen. (medscape.com)
  • Measure binding to amyloid protein of a group of benzothiazole derivatives already synthesized to expand the structure-activity relationship in this class of compounds. (sbir.gov)
  • and 2) radio-labeling with PET or SPECT radionuclides will provide a molecular probe that can image amyloid protein in vivo. (sbir.gov)
  • however, identical polypeptides can fold into multiple distinct amyloid conformations. (wikipedia.org)