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.
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.
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)
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
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.
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
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
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
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.
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.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
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.
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.
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.
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)
A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.
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.
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).
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.
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.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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.
A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.
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).
Proteins prepared by recombinant DNA technology.
A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
An 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.
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.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
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)
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.
The rate dynamics in chemical or physical systems.
The process of cleaving a chemical compound by the addition of a molecule of water.
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)
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.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
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.
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.
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Peptides composed of between two and twelve amino acids.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
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.
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.
Substances elaborated by specific strains of bacteria that are lethal against other strains of the same or related species. They are protein or lipopolysaccharide-protein complexes used in taxonomy studies of bacteria.
A cell line derived from cultured tumor cells.
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.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).
Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
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.
A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Peptides that have the ability to enter cells by crossing the plasma membrane directly, or through uptake by the endocytotic pathway.
The production of PEPTIDES or PROTEINS by the constituents of a living organism. The biosynthesis of proteins on RIBOSOMES following an RNA template is termed translation (TRANSLATION, GENETIC). There are other, non-ribosomal peptide biosynthesis (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT) mechanisms carried out by PEPTIDE SYNTHASES and PEPTIDYLTRANSFERASES. Further modifications of peptide chains yield functional peptide and protein molecules.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The thermodynamic interaction between a substance and WATER.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
The sum of the weight of all the atoms in a molecule.
Sites on an antigen that interact with specific antibodies.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Antibodies produced by a single clone of cells.
DNA analogs containing neutral amide backbone linkages composed of aminoethyl glycine units instead of the usual phosphodiester linkage of deoxyribose groups. Peptide nucleic acids have high biological stability and higher affinity for complementary DNA or RNA sequences than analogous DNA oligomers.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
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.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
A PEPTIDE of 22 amino acids, derived mainly from cells of VASCULAR ENDOTHELIUM. It is also found in the BRAIN, major endocrine glands, and other tissues. It shares structural homology with ATRIAL NATRIURETIC FACTOR. It has vasorelaxant activity thus is important in the regulation of vascular tone and blood flow. Several high molecular weight forms containing the 22 amino acids have been identified.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
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)
Peptides that regulate the WATER-ELECTROLYTE BALANCE in the body, also known as natriuretic peptide hormones. Several have been sequenced (ATRIAL NATRIURETIC FACTOR; BRAIN NATRIURETIC PEPTIDE; C-TYPE NATRIURETIC PEPTIDE).
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.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
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.
Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.
A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
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.
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Also known as CD104 antigen, this protein is distinguished from other beta integrins by its relatively long cytoplasmic domain (approximately 1000 amino acids vs. approximately 50). Five alternatively spliced isoforms have been described.
Neuropeptide and gut hormone that helps regulate GASTRIC ACID secretion and motor function. Once released from nerves in the antrum of the STOMACH, the neuropeptide stimulates release of GASTRIN from the GASTRIN-SECRETING CELLS.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC
A plant family of the order Liliales, subclass Liliidae, class Liliopsida (monocotyledon).
A 27-amino acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exact amino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is found in the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Transport proteins that carry specific substances in the blood or across cell membranes.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.
A group of FLAVONOLS based on kaempferol. They are derived from naringenin and can be hydroxylated to QUERCETIN or reduced to leucopelargonidin.
A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.
Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Diseases in which there is a familial pattern of AMYLOIDOSIS.
A computer simulation developed to study the motion of molecules over a period of time.
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Adherence of cells to surfaces or to other cells.
Measurement of the intensity and quality of fluorescence.

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (1/5562)

Amyloid fibrils are assemblies of misfolded proteins and are associated with pathological conditions such as Alzheimer's disease and the spongiform encephalopathies. In the amyloid diseases, a diverse group of normally soluble proteins self-assemble to form insoluble fibrils. X-ray fibre diffraction studies have shown that the protofilament cores of fibrils formed from the various proteins all contain a cross-beta-scaffold, with beta-strands perpendicular and beta-sheets parallel to the fibre axis. We have determined the threedimensional structure of an amyloid fibril, formed by the SH3 domain of phosphatidylinositol-3'-kinase, using cryo-electron microscopy and image processing at 25 A resolution. The structure is a double helix of two protofilament pairs wound around a hollow core, with a helical crossover repeat of approximately 600 A and an axial subunit repeat of approximately 27 A. The native SH3 domain is too compact to fit into the fibril density, and must unfold to adopt a longer, thinner shape in the amyloid form. The 20x40-A protofilaments can only accommodate one pair of flat beta-sheets stacked against each other, with very little inter-strand twist. We propose a model for the polypeptide packing as a basis for understanding the structure of amyloid fibrils in general.  (+info)

Dynamics of plaque formation in Alzheimer's disease. (2/5562)

Plaques that form in the brains of Alzheimer patients are made of deposits of the amyloid-beta peptide. We analyze the time evolution of amyloid-beta deposition in immunostained brain slices from transgenic mice. We find that amyloid-beta deposits appear in clusters whose characteristic size increases from 14 microm in 8-month-old mice to 22 microm in 12-month-old mice. We show that the clustering has implications for the biological growth of amyloid-beta by presenting a growth model that accounts for the experimentally observed structure of individual deposits and predicts the formation of clusters of deposits and their time evolution.  (+info)

Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats. (3/5562)

1. We have previously demonstrated that continuous i.c.v. infusion of amyloid beta-peptide (A beta), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory deficits in rats. 2. In the present study, we investigated the effects of nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on A beta-(1-42)-induced learning and memory deficits in rats. 3. In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were significantly impaired as compared with A beta-(40-1)-infused control rats. 4. Nefiracetam, at a dose range of 1-10 mg kg(-1), improved learning and memory deficits in the A beta-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5. Nefiracetam at a dose of 3 mg kg(-1) p.o. increased the activity of choline acetyltransferase in the hippocampus of A beta-(1-42)-infused rats. 6. Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A beta-(1-42)-infused rats, but failed to affect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7. These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease.  (+info)

Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis. (4/5562)

The genetic polymorphism of apolipoprotein E (apoE) is associated with the age of onset and relative risk of Alzheimer's disease (AD). In contrast to apoE3, the wild type allele, apoE4 confers an increased risk of late-onset AD. We demonstrate that the beta-amyloid peptide isoforms Abeta (1-28), Abeta (1-40), and Abeta (1-43) compete for the cellular metabolism of apoE3 and apoE4 containing beta-very low density lipoproteins. An antibody raised against Abeta (1-28) cross-reacted with recombinant apoE. Epitope mapping revealed positive amino acid clusters as common epitopes of Abeta (13 through 17; HHQKL) and apoE (residues 144 through 148; LRKRL), both regions known to be heparin binding domains. Abeta in which amino acids 13 through 17 (HHQKL) were replaced by glycine (GGQGL) failed to compete with the cellular uptake of apoE enriched betaVLDL. These observations indicate that Abeta and apoE are taken up into cells by a common pathway involving heparan sulfate proteoglycans.  (+info)

beta-amyloid load is not influenced by the severity of cardiovascular disease in aged and demented patients. (5/5562)

BACKGROUND AND PURPOSE: This study was conducted to analyze the association between reported risk factors for Alzheimer's disease, apolipoprotein E epsilon4 allele, and cardiovascular disease and neuropathological changes essential for the diagnosis of Alzheimer's disease. METHODS: Our data are based on clinical and postmortem evaluations of a cohort of nondemented (n=118) and demented (n=107) individuals. A cardiovascular index was calculated at autopsy to estimate the extent of cardiovascular disease. Neuropathological lesions such as senile/neuritic plaques, neurofibrillary tangles, beta-amyloid load, cerebral amyloid angiopathy, and the load of paired helical filaments were determined. RESULTS: The aforementioned neuropathological lesions did not show any positive significant correlation with cardiovascular index. In contrast, the extent of Alzheimer's lesions was significantly higher in those nondemented and demented patients carrying the apolipoprotein E epsilon4 allele than in those without this allele. CONCLUSIONS: Our results demonstrate that the apolipoprotein E epsilon4 allele, but not cardiovascular disease, indeed influences the extent of Alzheimer's lesions seen in the brain tissue of demented patients as well as asymptomatic controls.  (+info)

Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease. (6/5562)

Experimental studies indicate that overactivation of the DNA repair protein poly(ADP-ribose) polymerase (PARP) in response to oxidative damage to DNA can cause cell death due to depletion of NAD+. Oxidative damage to DNA and other macromolecules has been reported to be increased in the brains of patients with Alzheimer's disease. In the present study we sought evidence of PARP activation in Alzheimer's disease by immunostaining sections of frontal and temporal lobe from autopsy material of 20 patients and 10 controls, both for PARP itself and for its end-product, poly(ADP-ribose). All of the brains had previously been subjected to detailed neuropathological examination to confirm the diagnosis of Alzheimer's disease or, in the controls, to exclude Alzheimer's disease-type pathology. Double immunolabelling for poly(ADP-ribose) and microtubule-associated protein 2 (MAP2), glial fibrillary-acidic protein (GFAP), CD68, A beta-protein or tau was used to assess the identity of the cells with poly(ADP-ribose) accumulation and their relationship to plaques and neurofibrillary tangles. Both PARP- and poly(ADP-ribose)-immunolabelled cells were detected in a much higher proportion of Alzheimer's disease (20 out of 20) brains than of control brains (5 out of 10) (P = 0.0018). Double-immunolabelling for poly(ADP-ribose) and markers of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68, respectively) showed many of the cells containing poly(ADP-ribose) to be neurons. Most of these were small pyramidal neurons in cortical laminae 3 and 5. A few of the cells containing poly(ADP-ribose) were astrocytes. No poly(ADP-ribose) accumulation was detected in microglia. Double-immunolabelling for poly(ADP-ribose) and tau or A beta-protein indicated that the cells with accumulation of poly(ADP-ribose) did not contain tangles and relatively few occurred within plaques. Our findings indicate that there is enhanced PARP activity in Alzheimer's disease and suggest that pharmacological interventions aimed at inhibiting PARP may have a role in slowing the progression of the disease.  (+info)

Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein. (7/5562)

The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.  (+info)

The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein. (8/5562)

DP5, which contains a BH3 domain, was cloned as a neuronal apoptosis-inducing gene. To confirm that DP5 interacts with members of the Bcl-2 family, 293T cells were transiently co-transfected with DP5 and Bcl-xl cDNA constructs, and immunoprecipitation was carried out. The 30-kDa Bcl-xl was co-immunoprecipitated with Myc-tagged DP5, suggesting that DP5 physically interacts with Bcl-xl in mammalian cells. Previously, we reported that DP5 is induced during neuronal apoptosis in cultured sympathetic neurons. Here, we analyzed DP5 gene expression and the specific interaction of DP5 with Bcl-xl during neuronal death induced by amyloid-beta protein (A beta). DP5 mRNA was induced 6 h after treatment with A beta in cultured rat cortical neurons. The protein encoded by DP5 mRNA showed a specific interaction with Bcl-xl. Induction of DP5 gene expression was blocked by nifedipine, an inhibitor of L-type voltage-dependent calcium channels, and dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. These results suggested that the induction of DP5 mRNA occurs downstream of the increase in cytosolic calcium concentration caused by A beta. Moreover, DP5 specifically interacts with Bcl-xl during neuronal apoptosis following exposure to A beta, and its binding could impair the survival-promoting activities of Bcl-xl. Thus, the induction of DP5 mRNA and the interaction of DP5 and Bcl-xl could play significant roles in neuronal degeneration following exposure to A beta.  (+info)

TY - JOUR. T1 - Control of Alzheimers amyloid beta toxicity by the high molecular weight immunophilin FKBP52 and copper homeostasis in Drosophila. AU - Sanokawa-Akakura, Reiko. AU - Cao, Weihuan. AU - Allan, Kirsten. AU - Patel, Khyati. AU - Ganesh, Anupama. AU - Heiman, Gary. AU - Burke, Richard. AU - Kemp, Francis W.. AU - Bogden, John D.. AU - Camakaris, James. AU - Birge, Raymond B.. AU - Konsolaki, Mary. PY - 2010/1/13. Y1 - 2010/1/13. N2 - FK506 binding proteins (FKBPs), also called immunophilins, are prolyl-isomerases (PPIases) that participate in a wide variety of cellular functions including hormone signaling and protein folding. Recent studies indicate that proteins that contain PPIase activity can also alter the processing of Alzheimers Amyloid Precursor Protein (APP). Originally identified in hematopoietic cells, FKBP52 is much more abundantly expressed in neurons, including the hippocampus, frontal cortex, and basal ganglia. Given the fact that the high molecular weight ...
Metal binding to the amyloid beta-peptide is suggested to be involved in the pathogenesis of Alzheimers disease. We used high-resolution NMR to study zinc binding to amyloid beta-peptide 1-40 at physiologic pH. Metal binding induces a structural change in the peptide, which is in chemical exchange on an intermediate rate, between the apo-form and the holo-form, with respect to the NMR timescale. This causes loss of NMR signals in the resonances affected by the binding. Heteronuclear correlation experiments, N-15-relaxation and amide proton exchange experiments on amyloid beta-peptide 1-40 revealed that zinc binding involves the three histidines (residues 6, 13 and 14) and the N-terminus, similar to a previously proposed copper-binding site [Syme CD, Nadal RC, Rigby SE, Viles JH (2004) J Biol Chem279, 18169-18177]. Fluorescence experiments show that zinc shares a common binding site with copper and that the metals have similar affinities for amyloid beta-peptide. The dissociation constant K-d of ...
Recent preliminary data suggest that vaccination with Alzheimers Abeta might reduce senile plaque load and stabilize cognitive decline in human Alzheimers disease. To examine the mechanisms and consequences of anti-Abeta-antibody formation in a species more closely related to humans, rhesus monkeys (Macaca mulatta) were vaccinated with aggregated Abeta(1-42). Immunized monkeys developed anti-Abeta titers exceeding 1:1000, and their plasma Abeta levels were 5-10-fold higher than the plasma Abeta levels observed in monkeys vaccinated with aggregated amylin. These data support the use of non-human primates to model certain phenomena associated with vaccination of humans with aggregated Alzheimers Abeta. ...
Soluble oligomeric aggregates of the amyloid-beta peptide (Abeta) have been implicated in the pathogenesis of Alzheimers disease (AD). Although the conformation adopted by Abeta within these aggregates is not known, a beta-hairpin conformation is known to be accessible to monomeric Abeta. Here we show that this beta-hairpin is a building block of toxic Abeta oligomers by engineering a double-cysteine mutant (called Abetacc) in which the beta-hairpin is stabilized by an intramolecular disulfide bond. Abeta(40)cc and Abeta(42)cc both spontaneously form stable oligomeric species with distinct molecular weights and secondary-structure content, but both are unable to convert into amyloid fibrils. Biochemical and biophysical experiments and assays with conformation-specific antibodies used to detect Abeta aggregates in vivo indicate that the wild-type oligomer structure is preserved and stabilized in Abetacc oligomers. Stable oligomers are expected to become highly toxic and, accordingly, we find ...
Amyloid-beta peptide (Abeta) binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, is a cofactor facilitating Abeta-induced cell stress. We hypothesized that ABAD provides a direct link between Abeta and cytotoxicity via mitochondrial oxidant stress. Neurons cultured from …
Alzheimers disease (AD) is the most common cause of dementia and accounts for 50%-75% of all cases. It has been identified as a protein misfolding disease caused by plaque accumulation of abnormally folded beta amyloid and tau amyloid proteins in the brain.[2] Plaques are made up of small peptides, 39-43 amino acids in length, called beta-amyloid (Aβ) which is a fragment from a larger protein called amyloid precursor protein (APP), which is critical to neuron growth, survival and post-injury repair.[3][4] In AD, a proteolysis process causes APP to be divided into smaller fragments [5] which gives rise to fibrils of beta-amyloid that deposit outside neurons in dense formations known as senile plaques.[1][6]. Exactly how disturbances of production and aggregation of the beta-amyloid peptide gives rise to the pathology of AD is not known.[7][8 ...
The amyloid cascade hypothesis postulates that the initial event which triggers neuronal degradation in Alzheimers disease is enhanced amyloid-β generation and aggregation.
Amyloid beta-protein (Aβ) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimers disease. Aβ is known to increase free radical production in neur
There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimers disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-β exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-β on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-β and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-β on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of
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ABSTRACT: Alzheimer's disease (AD) is the most common cause of senile dementia worldwide. AD is a neurodegenerative disorder characterized by the loss of memory and language skill, collapse of the cognitive function, and distortion of social behavior. As of today, the onset mechanisms of AD and cure are unknown; however, three hallmarks are commonly encountered: extra and intracellular accumulation of amyloid beta (Abeta) peptide plaques, formation of intracellular neurofibrillary tangles, and inevitable neuronal death. Hypothetically, a possible scenario provoking or involved in the onset of AD is a cascade effect that starts with an imbalance in the production and clearance of Abeta peptide that consequently leads to its accumulation, formation of tau protein tangles and neuronal death. This work studied and characterized the mechanisms governing Abeta peptide aggregation and the effects of using anti-Abeta monoclonal antibodies to modify this process. These mechanisms play an important ...
Today, Crossbeta Biosciences and AdAlta announced that they have established a collaborative relationship in which AdAlta will deploy its i-body technology to develop oligomer-specific i-bodies for therapeutic and diagnostic applications in Alzheimers disease using Crossbetas stabilized beta-amyloid oligomers.. Alzheimers disease is the most common form of dementia, primarily affecting people above the age of 60. Over 26 million people are suffering from Alzheimers disease today, a number that is projected to triple over the coming 40 years. Alzheimers disease remains to be an area of great unmet need with huge and growing social and economic impact. Beta-amyloid oligomers are implicated in Alzheimers disease pathology and there is no effective treatment yet.. AdAltas innovative i-body technology represents the next generation of biological therapeutics merging the highly selective specificity of antibodies with the advantages of drug-like molecules, such as small size and extreme ...
TY - JOUR. T1 - Degradation of fibrillar forms of Alzheimers amyloid β-peptide by macrophages. AU - Majumdar, Amitabha. AU - Chung, Haeyong. AU - Dolios, Georgia. AU - Wang, Rong. AU - Asamoah, Nikiya. AU - Lobel, Peter. AU - Maxfield, Frederick R.. PY - 2008/5. Y1 - 2008/5. N2 - Cultured microglia internalize fibrillar amyloid Aβ (fAβ) and deliver it to lysosomes. Degradation of fAβ by microglia is incomplete, but macrophages degrade fAβ efficiently. When mannose-6 phosphorylated lysosomal enzymes were added to the culture medium of microglia, degradation of fAβ was increased, and the increased degradation was inhibited by excess mannose-6-phosphate, which competes for binding and endocytic uptake. This suggests that low activity of one or more lysosomal enzymes in the microglia was responsible for the poor degradation of fAβ. To further characterize the degradation of fAβ in late endosomes and lysosomes, we analyzed fAβ-derived intracellular degradation products in macrophages and ...
beta-Amyloid (Abeta) pathology is an essential pathogenic component in Alzheimers disease (AD). However, the significance of Abeta pathology, including Abeta deposits/oligomers and glial reactions, to neurodegeneration is unclear. In particular, despite the Abeta neurotoxicity indicated by in vitro studies, mouse models with significant Abeta deposition lack robust and progressive loss of forebrain neurons. Such results have fueled the view that Abeta pathology is insufficient for neurodegeneration in vivo. In this study, because monoaminergic (MAergic) neurons show degenerative changes at early stages of AD, we examined whether the APPswe/PS1DeltaE9 mouse model recapitulates progressive MAergic neurodegeneration occurring in AD cases. We show that the progression forebrain Abeta deposition in the APPswe/PS1DeltaE9 model is associated with progressive losses of the forebrain MAergic afferents. Significantly, axonal degeneration is associated with significant atrophy of cell bodies and ...
Alzheimers disease is characterized by the presence of neurotoxic beta amyloid (Aß) deposits in the brain. This article briefly explains the production of Aß from amyloid precursor protein (APP).
In Alzheimers disease (AD), abnormal accumulations of beta-amyloid are present in the brain and degenerating neurons exhibit cytoskeletal aberrations (neurofibrillary tangles). Roles for beta-amyloid in the neuronal degeneration of AD have been suggested based on recent data obtained in rodent studies demonstrating neurotoxic actions of beta- amyloid. However, the cellular mechanism of action of beta-amyloid is unknown, and there is no direct information concerning the biological activity of beta-amyloid in human neurons. We now report on experiments in human cerebral cortical cell cultures that tested the hypothesis that beta-amyloid can destabilize neuronal calcium regulation and render neurons more vulnerable to environmental stimuli that elevate intracellular calcium levels. Synthetic beta-amyloid peptides (beta APs) corresponding to amino acids 1-38 or 25-35 of the beta-amyloid protein enhanced glutamate neurotoxicity in cortical cultures, while a peptide with a scrambled sequence was ...
The role of lipids in the aggregation of three Alzheimer model peptides was investigated with circular dichroism spectroscopy and high-sensitivity titration calorimetry under conditions of low ionic strength. In solution, the peptides beta AP(25-35)OH and beta AP(25-35Nle)NH2 exhibit a reversible random-coilbeta-sheet (or beta-structured aggregate) transition. Addition of lipid vesicles containing negatively charged lipids shifts the random-coilbeta-sheet equilibrium almost completely toward beta-sheet structure, which can be explained by the specific conditions created at the membrane surface: the cationic peptides are attracted to the negatively charged membrane, and the increase in peptide concentration together with the partial alignment of the peptide molecules then facilitates beta-sheet formation. The third peptide, beta AP-(25-35)NH2, also binds to the lipid membrane but was found to adopt an essentially random-coil structure, both with and without lipids. A quantitative characterization ...
Readers,. Amyloid plaques and neurofibrillary tangles (NFTs) are the two classic hallmarks of Alzheimers disease (AD), but the connection between their two respective proteins-beta-amyloid and tau-has remained mysterious. Now, a paper published on July 21 in the prestigious journal Cell details a molecular mechanism that links tau to beta-amyloid toxicity at the synapse. The groundbreaking new study was led by Professor Jürgen Götz and Dr Lars Ittner, based at the University of Sydney.. Back in 2004, scientists from the University of California at Irvine injected anti-beta-amyloid antibodies in the brains of transgenic mice that develop both beta-amyloid deposits and NFTs. This treatment led to a rapid reduction of beta-amyloid deposits and reversed the accumulation of abnormal tau (Oddo et al., 2004). When the anti-beta-amyloid antibodies were removed, the beta-amyloid pathology re-emerged. This was followed by the reappearance of tau pathology. These findings from animal models provided ...
A non‐invasive intrinsic fluorescence sensing of the early stages of Alzheimers beta amyloid peptide aggregation in the presence of copper ions is reported. By using time‐resolved fluorescence techniques the formation of beta amyloid‐copper complexes and the accelerated peptide aggregation are demonstrated. The shifts in the emission spectral peaks indicate that the peptides exhibit different aggregation pathways than in the absence of copper.. ...
Beta-amyloid production results from cleavage in the extracellular domain of APP by the beta-secretase (BACE1) , which results in the production of the APP C-terminal fragment C99. This fragment is further cleaved by the gamma-secretase at residues 40-42 to produce beta-amyloid 40 and 42 peptides. Beta-amyloid aggregation and neuritic plaque formation are pathologic hallmarks of Alzheimer disease. This peptide corresponds to the human beta-amyloid 1-40 peptide ...
Although the amyloid hypothesis offers a broad framework to explain AD pathogenesis, it is currently lacking in detail, and certain observations do not fit easily with the simplest version of the hypothesis. The most frequently voiced objection is that the number of amyloid deposits in the brain does not correlate well with the degree of cognitive impairment that the patient experienced in life. Indeed, some humans without symptoms of AD have many cortical Aβ deposits. However, the latter are almost exclusively diffuse forms of amyloid plaques that are not associated with surrounding neuritic and glial pathology. Such diffuse Aβ deposits may be analogous to early fatty streaks of cholesterol that are the harbingers of mature, symptom-producing atherosclerotic plaques. Moreover, the degree of dementia in AD correlates much better with Aβ assayed biochemically than with histologically determined plaque counts, and the concentration of soluble Aβ species (which are invisible to ...
Although the amyloid hypothesis offers a broad framework to explain AD pathogenesis, it is currently lacking in detail, and certain observations do not fit easily with the simplest version of the hypothesis. The most frequently voiced objection is that the number of amyloid deposits in the brain does not correlate well with the degree of cognitive impairment that the patient experienced in life. Indeed, some humans without symptoms of AD have many cortical Aβ deposits. However, the latter are almost exclusively diffuse forms of amyloid plaques that are not associated with surrounding neuritic and glial pathology. Such diffuse Aβ deposits may be analogous to early fatty streaks of cholesterol that are the harbingers of mature, symptom-producing atherosclerotic plaques. Moreover, the degree of dementia in AD correlates much better with Aβ assayed biochemically than with histologically determined plaque counts, and the concentration of soluble Aβ species (which are invisible to ...
TY - JOUR. T1 - RS-0406 arrests amyloid-b oligomer-induced behavioural deterioration in vivo. AU - OHare, Eugene. AU - Scopes, David I C. AU - Treherne, Mark J. AU - Norwood, Kelly. AU - Spanswick, David. AU - Kim, Eun-Mee. PY - 2010. Y1 - 2010. U2 - 10.1016/j.bbr.2010.01.044. DO - 10.1016/j.bbr.2010.01.044. M3 - Article. VL - 210. SP - 32. EP - 37. JO - Behavioural Brain Research. JF - Behavioural Brain Research. SN - 0166-4328. ER - ...
The purpose of this work is the reduction in the Abeta amyloid peptide burden in brain of Alzheimers disease (AD) transgenic mice without the concomitant elevation in plasma Abeta amyloid peptide. APPswe,PSEN1dE9 mice were studied at 12 months of age. The mice were shown to have considerable Abeta amyloid plaques in cerebral cortex based on immunocytochemistry. The mice were treated every 3C4 days by intravenous injections of either saline or the cTfRMAb-ScFv fusion protein at an injection dose of 1 1 mg/kg for 12 consecutive weeks. The brain A1C42 concentration was reduced 40% in the fusion protein treated mice, without any elevation in plasma A1C42 concentration. No cerebral micro-hemorrhage was observed in the treated mice. These results display that brain-penetrating antibody pharmaceutics can be developed for mind disorders such as AD TAE684 following a re-engineering of the antibody like a fusion protein that is transferred across the BBB via receptor-mediated transport. Keywords: ...
Transgenic mouse models that overexpress APP develop senile plaques over time that resemble those found in human Alzheimers disease. These animals are a valuable tool toward understanding the physiology and pathology of senile plaques in living tissue and are ideal for evaluating therapeutics aimed at clearance of amyloid-β deposits in the brain. With the recent success using immunotherapy for prevention of amyloid-β deposits in these animals (Schenk et al., 1999; Bard et al., 2000), as well as clearance of existing plaques (Bacskai et al., 2001), this treatment seems very promising. Recent reports have also indicated that immunotherapy may have positive effects on behavioral deficits exhibited in transgenic mouse models (Janus et al., 2000; Morgan et al., 2000). These findings are important for predicting whether anti-amyloid therapies will prove beneficial not just in arresting deposition of amyloid-β but also in prevention of the associated dementia. Microglial cells were implicated in ...
Antibodies , OptimAb Antibodies , OptimAbᵀᴹ Beta-Amyloid 17-24 , Monoclonal Antibody, purified; Beta-Amyloid forms are deposited in the CNS of patients with Alzheimer s disease and Down s syndrome. Biochemical analysis of the amyloid peptides isolated from Alzheimer s disease brain indicates that Beta-Amyloid (1-42) is the principal species associated with senile plaque amyloids, while Beta-Amyloid (1-40) is more abundant in cerebrovascular amyloid deposits. Both result from the cleavage of Amyloid Precursor Protein (APP) by secretases. The mAb 4G8 reacts to the abnormally processed isoforms, as well as precursor forms.; Host:MouseClone: 4G8Isotype: IgG2bReactivity: Human, MouseImmunogen: This antibody is reactive to residues 17-24 of Beta-Amyloid. The epitope lies within amino acids 18-22 of Beta-Amyloid (VFFAE)Concentration:1 mg/mLFormulation:PBS (no preservatives); The Ab was purified on Protein GApplications:The Ab is effective in immunoblotting (WB),
Amyloid-β PET and CSF Aβ42 yield discordant results in 10-20% of memory clinic patients, possibly providing unique information. Although the predictive power of demographic, clinical, genetic, and imaging features for amyloid positivity has previously been investigated, it is unknown whether these features differentially predict amyloid-β status based on PET or CSF or whether this differs by disease stage. We included 768 patients (subjective cognitive decline (SCD, n = 194), mild cognitive impairment (MCI, n = 127), dementia (AD and non-AD, n = 447) with amyloid-β PET and CSF Aβ42 measurement within 1 year. Ninety-seven (13%) patients had discordant PET/CSF amyloid-β status. We performed parallel random forest models predicting separately PET and CSF status using 17 patient features (demographics, APOE4 positivity, CSF (p)tau, cognitive performance, and MRI visual ratings) in the total patient group and stratified by syndrome diagnosis. Thereafter, we selected features with the highest variable
The search for effective therapies and early detection strategies for Alzheimers Disease (AD), the major cause of dementia in Europe, is imperative. It is known that beta-amyloid (Abeta) peptide plays a central role in neurodegeneration. In AD brain, Abeta is released in a soluble form that progressively becomes insoluble forming aggregates; extracellular plaques mainly composed of Abeta are a hallmark of post-mortem brains. These premises strongly suggest brain Abeta as a possible target for therapy and diagnosis of AD. In addition, it is known that brain and blood Abeta pools are in equilibrium via the blood-brain-barrier (BBB). Accordingly, it has been reported that removal of blood Abeta may withdraw the excess of brain Abeta by a sink effect. Thus, blood Abeta is another potential target. The aim of this project is to utilize nanoparticles (NPs) specifically engineered for targeting brain Abeta, for the combined diagnosis and therapy (theranostics) of AD. NPs (liposomes, solid lipid NPs, ...
Alzheimers disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18) in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress. We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP) and its processing products, its cleaving enzymes, involved in amyloidogenic processing of
in Journal of Neurochemistry (2010), 114(2), 576-586. Alzheimers disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Abeta) complexes or senile plaques. Abeta peptide is firstly produced as monomers, readily ... [more ▼]. Alzheimers disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Abeta) complexes or senile plaques. Abeta peptide is firstly produced as monomers, readily aggregating to form multimeric complexes, of which the smallest aggregates are known to be the most neurotoxic. In AD patients, abundant reactive microglia migrate to and surround the Abeta plaques. Though it is well known that microglia are activated by Abeta, little is known about the peptide conformation and the signaling cascades responsible for this activation. In this study, we have stimulated murine microglia with different Abeta(1-42) forms, inducing an inflammatory state, which was peptide conformation-dependent. The ...
Sigma-Aldrich offers abstracts and full-text articles by [Juliet A Moncaster, Roberto Pineda, Robert D Moir, Suqian Lu, Mark A Burton, Joy G Ghosh, Maria Ericsson, Stephanie J Soscia, Anca Mocofanescu, Rebecca D Folkerth, Richard M Robb, Jer R Kuszak, John I Clark, Rudolph E Tanzi, David G Hunter, Lee E Goldstein].
P05067: Amyloid beta A4 protein; ABPP; APPI; APP; Alzheimer disease amyloid protein; Cerebral vascular amyloid peptide; CVAP; PreA4; Protease nexin-II; PN-II; N-APP; Soluble APP-alpha; S-APP-alpha; Soluble APP-beta; S-APP-beta; C99; Beta-amyloid protein 42; Beta-APP42; Beta-amyloid protein 40; Beta-APP40; C83; P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59; Amyloid intracellular domain 59; AICD-59; AID(59); Gamma-CTF(59); Gamma-secretase C-terminal fragment 57; Amyloid intracellular domain 57; AICD-57; AID(57); Gamma-CTF(57); Gamma-secretase C-terminal fragment 50; Amyloid intracellular domain 50; AICD-50; AID(50); Gamma-CTF(50); C31; ...
Live discussion held 5 December 2001, noon-1 p.m. (EST).. Participants: Dick Lloyd, Sam Gandy, June Kinoshita, Richard Bowen, Nico Stanculescu, Seth Shaw, Mark Smith, Steve Fiander, Gunnar Gouras, Larry Tusick, Alan Lerner, Alexei R. Koudinov, Mike Shelanski, Rena Li, Gabrielle Strobel, Craig Atwood, and the mysterious Guest 2.. Note: The transcript has been edited for clarity and accuracy.. June: First, let me welcome you all to todays live discussion.. Sam Gandy: Thanks for organizing it, June.. June: I know that Richard Bowen has been eager to discuss some of the points in your discussion. Richard, would you like to ask the first question?. Richard L. Bowen: Yes, June: I wanted to know if Sam has looked at the ovariectomized mice and beta amyloid study, and have you had a chance to look at gonadotrophin levels?. Sam Gandy: We havent studied gonadotrophin levels under any circumstances. A paper on ovariectomy effects on Ab load in transgenic mice is in press at J. Neurochem. Co-authors are ...
Physical exercise has been suggested to reduce the risk of developing Alzheimers disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse model of AD did not affect levels of soluble amyloid beta (Aβ), synaptic proteins or cognitive function. In this follow-up study, we investigate whether running could impact other pathological aspects of the disease, such as insoluble Aβ levels, the neuroinflammatory response and non-cognitive behavioral impairments. We investigated the effects of 24 weeks of voluntary wheel running in female 5xFAD mice (n = 30) starting at 2-3 months of age, before substantial extracellular plaque formation. Running mice developed hindlimb clasping earlier (p = 0.009) compared to sedentary controls. Further, running exacerbated the exploratory behavior in Elevated plus maze
Dear Amyloid/Ageing subscribers: I began to study Alzheimers amyloid beta (Ab) protein in 1992, at the time when it was becoming clear that this protein exists normally in a soluble form (soluble Ab) and that it is not just a pathological protein. My research activities yielded an on-going project, devoted to understanding in more detail the normal biology of amyloid beta. Understanding the normal biology of Ab would answer the questions of why soluble Ab does not undergo fibrillogenesis in biological fluids but does polymerize into amyloid fibrils in the disease, and what the biological consequences of Ab deposition within the brain tissue are. This, in turn, would be crucial for understanding the pathophysiology of Alzheimers disease and for delineating pathologically grounded new approaches to therapy. My current postdoctoral position at NYU Medical Center just expired. Thus, to continue my research I have to find another position. I would be happy to continue my research as a part of your ...
Beta-amyloid is a protein fragment at the focus of research into the causes of Alzheimers disease. It is normally found in the brain but during the disease process, it forms small clumps known as oligomers, which are thought to be toxic to nerve cells. Eventually, beta-amyloid oligomers combine to form even larger structures known as fibrils, which then form amyloid plaques in the brain, one of the characteristic features of Alzheimers disease. Stephen Meredith, M.D., Ph.D., and colleagues have been studying the detailed molecular structure of beta-amyloid fibrils and working to identify what may trigger their development in Alzheimers disease. They have found that fibrils can have different structures from one person to the next, but that the fibrils found in different parts of the brain of a single person are generally the same. The researchers hypothesize that formation of an initial oligomer or fibril in one area of the brain may trigger the accumulation of other oligomers and subsequent ...
Immunotherapy for Alzheimers disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Abeta), which circulate in the bloodstream and remove Abeta from the brain. In mouse models of AD, the administration of anti-Abeta antibodies directly into the brain, in comparison to the bl …
Product Name: Amyloid beta-Protein (Human, 34-40) Antiserum (50 ul vial) Product Number: NAB-14356-v Synonym(s): Amyloid beta-Protein (1-40) Specific Antiserum (Rabbit) Antiserum Application: Our undiluted antisera are suitable for immuno-histochemical use, for application to radioimmunoassay (RIA), or other non-isotop
In the field of neurobiology, there is great discussion about which particular species of amyloid-beta oligomers (AβOs) contributes to the pathogenesis of Alzheimers disease (AD), a progressive neurodegenerative disease. Previously, our group has found, using molecular weight cutoff filters (MWCO), that AβOs are primarily 100-300 kilodaltons (kDa). The goal of this project is to verify this finding using size exclusion chromatography (SEC). SEC can be used to determine AβO molecular weight according to the amount of time it takes the AβOs to pass through the SEC column. Overall, the project yielded results showing significant portion of AβOs are either |1300 kDa or around 13 kDa. We are currently investigating further reasons why the MWCO and SEC data yield very different results.
Proteolytic cleavage of amyloid-β-protein precursor (AβPP) by β- and γ-secretases results in production of the amyloid-β peptide (Aβ) that accumulates in the brains of sufferers of Alzheimers disease (AD). We have developed a monoclonal antibody, 2B
Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. GTP hydrolysis in protein synthesis: two for Tu?
Soluble β-amyloid peptide (βAP) is measured in biological fluids at very low concentrations, typically in the range from 0.1 ng/ml to 10 ng/ml. The measurement of βAP concentrations in animals or conditioned medium from cultured cells can be used for drug screening, where test compounds are administered to the animals or exposed to the cultured cells and the accumulation of βAP in the animal or culture medium observed. It has been found that elevated levels of βAP in body fluids, such as blood and cerebrospinal fluid, is associated with the presence of a βAP-related condition in a patient, such as Alzheimers Disease. Methods for diagnosing and monitoring βAP-related conditions comprise measuring the levels of βAP in such body fluids from a patient.
My research is focussed on Alzheimers Drug Discovery and compounds that modify amyloid fibril toxicity. I have discovered amyloid peptide interactions with the Kisspeptin, Kissorphin and Neuropeptide-FF peptides, which prevent the toxicity of the amyloid peptides in vitro. I discovered that endocannabinoids are neuroprotective against the Alzheimers Amyloid-beta peptide in vitro. I have characterized interactions between amyloid peptides and the enzymes Catalase and Cyclin-Dependent-Kinase-1.. ...
Alzheimers disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-ß plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimers disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-ß pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-ß deposition in the progression from ageing to Alzheimers disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20-93 years; 47 amyloid-ß-positive) and 20 amyloid-ß-positive patients with mild cognitive impairment or Alzheimers disease ...
TY - JOUR. T1 - Always around, never the same. T2 - Pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimers disease. AU - Hoozemans, Jeroen J M. AU - Chafekar, Sidhartha M.. AU - Baas, Frank. AU - Eikelenboom, Piet. AU - Scheper, Wiep. PY - 2010/1/1. Y1 - 2010/1/1. N2 - There is an increasing amount of evidence showing the importance of intermediate aggregation species of amyloid β (Aβ) in the pathogenic cascade of Alzheimers disease (AD). Different Aβ assembly forms may mediate diverse toxic effects at different stages of the disease. Mouse models for AD suggest that intraneuronal accumulation of Aβ oligomers might be involved in AD pathogenesis at a very early stage of the disease. The detrimental effect of oligomeric Aβ on synaptic efficacy is suggested to be an early event in the pathogenic cascade. Also early neuronal responses as activation of the unfolded protein response are processes likely to be associated with the increased occurrence ...
misc{6494bef1-596c-4a8f-a511-b3b2760e7a57, author = {Linse, Sara and Thulin, Eva and Hellstrand, Erik and Sparr, Emma and Walsh, D.}, issn = {1742-464X}, language = {eng}, note = {Conference Abstract}, pages = {11--11}, publisher = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd}, series = {The FEBS Journal}, title = {Towards physico-chemical understanding of fibril formation of the Alzheimer disease-associated amyloid beta-peptide}, volume = {276}, year = {2009 ...
21st Century Biochemicals - Catalog: Beta Amyloid Peptides (also known as: Abeta peptides | Amyloid beta A4 | A beta P | amyloid beta-peptide | aa 1-40/42)
Osborne, C and West, E and Nolan, W and McHale-Owen, H and Williams, A and Bate, C (2016) Glimepiride protects neurons against amyloid-beta-induced synapse damage. NEUROPHARMACOLOGY, 101. pp. 225-236. ...
The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimers disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Downs syndrome postmortem brain tissue. Importantly, Abeta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Abeta. We have recently shown that intraneuronal accumulation of Abeta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Abeta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for Abeta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque ...
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Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimers disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered ...
TY - JOUR. T1 - Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimers disease-like neuropathology. AU - Bard, Frédérique. AU - Barbour, Robin. AU - Cannon, Catherine. AU - Carretto, Robert. AU - Fox, Michael. AU - Games, Dora. AU - Guido, Teresa. AU - Hoenow, Kathleen. AU - Hu, Kang. AU - Johnson-Wood, Kelly. AU - Khan, Karen. AU - Kholodenko, Dora. AU - Lee, Celeste. AU - Lee, Mike. AU - Motter, Ruth. AU - Nguyen, Minh. AU - Reed, Amanda. AU - Schenk, Dale. AU - Tang, Pearl. AU - Vasquez, Nicki. AU - Seubert, Peter. AU - Yednock, Ted. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2003/2/18. Y1 - 2003/2/18. N2 - Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor protein, exhibit CNS pathology that is similar to Alzheimers disease. In an age-dependent fashion, the mice develop plaques containing β-amyloid peptide (Aβ) and exhibit neuronal dystrophy and synaptic loss. It has ...
Yazawa H., Yu Z.-X., Takeda K., Le Y., Gong W., Ferrans V.J., Oppenheim J.J., Li C.C.H., Wang J.M.. The 42 amino acid form of beta amyloid (Abeta42) plays a pivotal role in neurotoxicity and the activation of mononuclear phagocytes in Alzheimers disease (AD). Our recent study revealed that FPRL1, a G-protein-coupled receptor, mediates the chemotactic and activating effect of Abeta42 on mononuclear phagocytes (monocytes and microglia), suggesting that FPRL1 may be involved in the proinflammatory responses in AD. We investigated the role of FPRL1 in cellular uptake and the subsequent fibrillar formation of Abeta42 by using fluorescence confocal microscopy. We found that upon incubation with macrophages or HEK293 cells genetically engineered to express FPRL1, Abeta42 associated with FPRL1 and the Abeta42/FPRL1 complexes were rapidly internalized into the cytoplasmic compartment. The maximal internalization of Abeta42/FPRL1 complexes occurred by 30 min after incubation. Removal of free Abeta42 from ...
TY - JOUR. T1 - Abnormal interaction of oligomeric amyloid-β with phosphorylated tau. T2 - Implications to synaptic dysfunction and neuronal damage. AU - Manczak, Maria. AU - Reddy, P (Hemachandra). PY - 2013. Y1 - 2013. N2 - Alzheimers disease (AD) is a progressive neurodegenerative mental illness characterized by memory loss, multiple cognitive impairments, and changes in personality and behavior. The purpose of our study was to determine the interaction between monomeric and oligomeric amyloid-β (Aβ) and phosphorylated tau in AD neurons. Using postmortem brains from AD patients at different stages of disease progression and control subjects, and also from AβPP, AβPPxPS1, and 3xTg-AD mice, we studied the physical interaction between Aβ and phosphorylated tau. Using immunohistological and double-immunofluorescence analyses, we also studied the localization of monomeric and oligomeric Aβ with phosphorylated tau. We found monomeric and oligomeric Aβ interacted with phosphorylated tau in ...
As has been described in naturally occurring CAA (1, 5), vascular amyloid deposition in APP23 mice is most frequently found in arteries/arterioles and occurs most often in vessels outside the brain parenchyma proper (e.g., pia, fissures). The arterial predilection suggests that an anatomical difference between arteries and veins (e.g., presence of significant amounts of smooth muscle) could contribute to the development of CAA. Indeed, it has been hypothesized that Aβ is deposited by vascular smooth muscle cells and/or perivascular microglia, and APP expression and Aβ production by vascular cells have been well documented (22, 23). These reports and the observation that vessels apart from the neuropil are more often affected strongly implicate local production or circulating Aβ as an important source, although these hypotheses fail to explain the exclusive localization of CAA to cerebral vessels. In the present study, through examination of APP transgenic mice on an App-null background, we ...
The ε4 allele of apolipoprotein E (ApoE) accounts for an estimated 45-60% of the genetic risk for late onset sporadic Alzheimers disease, suggesting that it may be possible to identify other genetic loci that could account for the remaining risk associated with this disease. Recently, a biallelic polymorphism (G/A) in the 3′ untranslated region (UTR) of the transcription factor LBP-1c/CP2/LSF (for brevity, CP2) has been implicated in Alzheimers disease susceptibility, with the 3′-UTR A allele being associated with a reduction in the risk of sporadic Alzheimers disease.1-3 The CP2 gene is a plausible candidate for influencing Alzheimers disease risk: it is located near the LDL receptor related protein gene within the Alzheimers disease linkage region on chromosome 12; it controls the expression of several genes (α2 macroglobulin, glycogen synthase kinase-3β); and it interacts with different proteins (serum amyloid A3, interleukin 1α, tumour necrosis factor α, and Fe65 protein) and ...
PubMedID: 25947203 | Platelet dysfunction in hypercholesterolemia mice, two Alzheimers disease mouse models and in human patients with Alzheimers disease. | Biogerontology | 8/1/2015
The pathological mechanisms underlying Alzheimers disease (AD) are still not understood. The disease pathology is characterized by accumulation and aggregation of amyloid-β (Aβ) peptides into extracellular plaques, however the factors that promote neurotoxic Aβ aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides and proteins in biological tissues. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) based imaging was used to study Aβ deposition in transgenic mouse brain tissue and to elucidate the plaque associated chemical microenvironment. The imaging experiments were performed in brain sections of transgenic Alzheimers disease mice carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe). Multivariate image analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical
Alzheimers disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specfically the more amyloidogenic form, Abeta42. ...
Synonyms: Amyloid Beta A4 Protein, APPI, ABPP, Alzheimer Disease Amyloid Protein, Beta-amyloid Precursor Protein, Cerebral Vascular Amyloid Peptide, CVAP, PreA4, Protease Nexin-II, PN-II ...
in Journal of Biological Chemistry (1996), 271(46), 28757-65. A series of natural peptides and mutants, derived from the Alzheimer beta-amyloid peptide, was synthesized, and the potential of these peptides to induce fusion of unilamellar lipid vesicles was ... [more ▼]. A series of natural peptides and mutants, derived from the Alzheimer beta-amyloid peptide, was synthesized, and the potential of these peptides to induce fusion of unilamellar lipid vesicles was investigated. These peptide domains were identified by computer modeling and correspond to respectively the C-terminal (e.g. residues 29-40 and 29-42) and a central domain (13-28) of the beta-amyloid peptide. The C-terminal peptides are predicted to insert in an oblique way into a lipid membrane through their N-terminal end, while the mutants are either parallel or perpendicular to the lipid bilayer. Peptide-induced vesicle fusion was demonstrated by several techniques, including lipid-mixing and core-mixing assays using pyrene-labeled ...
in Journal of Biological Chemistry (1996), 271(46), 28757-65. A series of natural peptides and mutants, derived from the Alzheimer beta-amyloid peptide, was synthesized, and the potential of these peptides to induce fusion of unilamellar lipid vesicles was ... [more ▼]. A series of natural peptides and mutants, derived from the Alzheimer beta-amyloid peptide, was synthesized, and the potential of these peptides to induce fusion of unilamellar lipid vesicles was investigated. These peptide domains were identified by computer modeling and correspond to respectively the C-terminal (e.g. residues 29-40 and 29-42) and a central domain (13-28) of the beta-amyloid peptide. The C-terminal peptides are predicted to insert in an oblique way into a lipid membrane through their N-terminal end, while the mutants are either parallel or perpendicular to the lipid bilayer. Peptide-induced vesicle fusion was demonstrated by several techniques, including lipid-mixing and core-mixing assays using pyrene-labeled ...
TY - GEN. T1 - Release of β-amyloid from high-density platelets. T2 - Implications for Alzheimers disease pathology. AU - Casoli, Tiziana. AU - Di Stefano, Giuseppina. AU - Giorgetti, Belinda. AU - Grossi, Yessica. AU - Balietti, Marta. AU - Fattoretti, Patrizia. AU - Bertoni-Freddari, Carlo. PY - 2007/1. Y1 - 2007/1. N2 - The main component of Alzheimers disease (AD) senile plaques in the brain is amyloid-β peptide (Aβ), a proteolytic fragment of the amyloid precursor protein (APP). Platelets contain both APP and Aβ and much evidence suggests that these cells may represent a useful tool to study bothamyloidogenic and nonamyloidogenic pathways of APP processing. It has been demonstrated that platelets activated by physiological agonists, such as thrombin and collagen, specifically secrete Aβ ending at residue 40. To verify whether APP β-processing could be observed also in an in vitro system of highly concentrated platelets, we measured the Aβ released in the incubation media of 5 ± ...
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], ...
Purpose: : Our lab has been investigating the striking degree of shared cell biology, developmental mechanisms, and gene expression in lens and brain, to understand shared mechanisms of age-related degenerative disease fundamental to both tissues. Work from this, and now from other, laboratories highlight a fundamental role for Alzheimer proteins in lens age-related disease. Moreover, this fundamental link can be exploited for diagnosis of the onset and severity of AD in brain. Considerable evidence in AD research demonstrates that system-wide factors in the body, and most strikingly high cholesterol in the diet together with copper bioavailabilty, have a key role in determining onset and severity of AD brain pathology in humans and in animal models. Further these factors are also critical determinants of cataract formation in the lens. Here we examined the role of Alzheimer proteins in animals on high cholesterol diet with 0.12 ppm Cu in water (10-fold under EPA standards for humans). Methods: ...
Brendel M., Kleinberger G., Probst F., Jaworska A., Overhoff F., Blume T., Albert NL., Carlsen J., Lindner S.; Gildehaus FJ., Ozmen L., Suárez-Calvet M., Bartenstein P., Baumann K., Ewers M., Herms J., Haass C., Rominger A. (2017) Increase of TREM2 during Aging of an Alzheimers Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis. Front Aging Neurosci. 9:8. Rammes G., Mattusch C.; Wulff M., Seeser F., Kreuzer M., Zhu K., Deussing JM., Herms J., Parsons, CG. (2017) Involvement of GluN2B subunit containing N-methyl-d-aspartate (NMDA) receptors in mediating the acute and chronic synaptotoxic effects of oligomeric amyloid-beta (Aβ) in murine models of Alzheimers disease (AD). Neuropharmacology. [Epub ahead of print]. Blazquez-Llorca L., Valero-Freitag S., Rodrigues EF., Merchán-Pérez Á., Rodríguez JR., Dorostkar MM., DeFelipe J., Herms J. (2017) High plasticity of axonal pathology in Alzheimers disease mouse models. Acta Neuropathol Commun. 5(1):14. Zhu K. Xiang X., ...
The β-amyloid peptide (Aβ) may be the major constituent from the amyloid core of senile plaques within the mind of patients with Alzheimers disease (AD). resulted in a drastic reduced amount of Aβ42 and Aβ40 secretion. β-Cleavage of mutant APP HOE 32021 had not been inhibited and reduced amount of Aβ secretion resulted from inhibition of γ-cleavage. It had been anticipated that reduced γ-cleavage of mutant APP would derive from inhibition of its dimerization. Amazingly mutations from the GxxxG theme actually improved dimerization from the APP C-terminal fragments perhaps with a different TM α-helical user interface. Increased dimerization from the TM APP C-terminal area did not have an effect on AICD creation. These results obviously demonstrate that both orientation and dimerization from the APP TM area differently have an effect on Aβ and AICD creation. The intensifying deposition of β-amyloid peptide (Aβ)1 resulting in the forming of senile plaques can be an invariant feature of ...
Background: The cerebrospinal fluid (CSF) amyloid-β (Aβ)1-42, total-tau (T-tau), and phosphorylated-tau (P-tau181P) profile has been established as a valuable biomarker for Alzheimers disease (AD). Objective: The current study aimed to determine CSF biomarker cut-points using positron emission tomography (PET) Aβ imaging screened subjects from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, as well as correlate CSF analyte cut-points across a range of PET Aβ amyloid ligands. Methods: Aβ pathology was determined by PET imaging, utilizing 11C-Pittsburgh Compound B, 18F-flutemetamol, or 18F-florbetapir, in 157 AIBL participants who also underwent CSF collection. Using an INNOTEST assay, cut-points were established (Aβ1-42 ,544 ng/L, T-tau ,407 ng/L, and P-tau181P ,78 ng/L) employing a rank based method to define a positive CSF in the sub-cohort of amyloid-PET negative healthy participants (n = 97), and compared with the presence of PET demonstrated AD pathology. ...
Calcium: A proven target in the war on Alzheimers disease Alzheimers disease is practically a household word these days, as the number of individuals dia
Abnormal production and accumulation of amyloid-β peptide (Aβ) plays a major role in the pathogenesis of Alzheimers disease (AD). β-secretase (BACE1) is responsible for the cleavage at the β-site in amyloid β protein precursor (AβPP/APP) to generate
Alzheimers disease (AD) is the most common cause of dementia in adults and is characterised at the microscopic level by extracellular amyloid plaques and intraneuronal tau tangles. Amyloid plaques are composed of fibrillar aggregates of a spectrum of amyloid beta (Aβ) peptides derived from the proteolytic cleavage of amyloid precursor protein (APP) (LaFerla et al., 2007). The significance of Aβ is underpinned by the numerous disease-linked mutations that dysregulate APP processing: mutations that result in a spectrum of Aβ peptides with a higher aggregation propensity have been linked to familial AD (Philipson et al., 2010), whereas sequence variation in APP that reduces Aβ production is protective (Jonsson et al., 2012). There is much evidence from cell-culture and animal-model systems (Iijima-Ando and Iijima, 2010; Philipson et al., 2010) that the conformers of Aβ that possess neurotoxic activity are likely to be soluble oligomeric species rather than the more easily detected amyloid ...
Chalmers, K., Blomqvist, M.-L., Andreasen, N., Bogdanovic, N. and Wilcock, G. (2005) Sequence variants of IDE are associated with the extent of beta-amyloid deposition in the Alzheimers disease brain. Neurobilogy of Aging, 26 (6). pp. 795-802. ISSN 0197-4580 Available from: Full text not available from this repository. Publishers URL: ...
Alzheimer disease 3 (AD3) [MIM:607822]: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269,PubMed:10025789, ECO:0000269,PubMed:10090481, ECO:0000269,PubMed:10200054, ECO:0000269,PubMed:10208579, ECO:0000269,PubMed:10439444, ECO:0000269,PubMed:10441572, ECO:0000269,PubMed:10447269, ECO:0000269,PubMed:10533070, ECO:0000269,PubMed:10631141, ECO:0000269,PubMed:10644793, ECO:0000269,PubMed:11027672, ...
Alzheimer disease 3 (AD3) [MIM:607822]: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269,PubMed:10025789, ECO:0000269,PubMed:10090481, ECO:0000269,PubMed:10200054, ECO:0000269,PubMed:10208579, ECO:0000269,PubMed:10439444, ECO:0000269,PubMed:10441572, ECO:0000269,PubMed:10447269, ECO:0000269,PubMed:10533070, ECO:0000269,PubMed:10631141, ECO:0000269,PubMed:10644793, ECO:0000269,PubMed:11027672, ...
Neurodegeneration is characterized by dysfunction and death of cells in the nervous system. This results in impaired motor function and progressive dementia. Neurodegenerative diseases include prion disease, Parkinsons disease, Huntingtons disease, Amyotrophic Lateral Sclerosis (Lou Gehrigs disease), and various types of dementia, of which Alzheimers disease is the most common. Intense research focus on Alzheimers disease has identified 2 main pathways leading to characteristic protein deposits in the brain. These are pathologic breakdown of amyloid precursor protein leading to the formation of extracellular amyloid plaques, and hyperphosphorylation of the microtubule associated protein Tau, causing intracellular neurofibrillary tangles. Several genes have confirmed links to Alzheimers disease, and many genotyping and gene expression studies currently in progress aim to elucidate the causes, develop biomarkers for diagnosis, and identify potential drug targets ...
Neurodegeneration is characterized by dysfunction and death of cells in the nervous system. This results in impaired motor function and progressive dementia. Neurodegenerative diseases include prion disease, Parkinsons disease, Huntingtons disease, Amyotrophic Lateral Sclerosis (Lou Gehrigs disease), and various types of dementia, of which Alzheimers disease is the most common. Intense research focus on Alzheimers disease has identified 2 main pathways leading to characteristic protein deposits in the brain. These are pathologic breakdown of amyloid precursor protein leading to the formation of extracellular amyloid plaques, and hyperphosphorylation of the microtubule associated protein Tau, causing intracellular neurofibrillary tangles. Several genes have confirmed links to Alzheimers disease, and many genotyping and gene expression studies currently in progress aim to elucidate the causes, develop biomarkers for diagnosis, and identify potential drug targets ...
Recombinant Human Amyloid Precursor Protein Protein fragment datasheet (ab124588). Abcam offers quality products including antibodies, assays and other…
During the past decade my interest have focused on the pathogenesis of Alzheimers disease, one of the most destructive neurological diseases that affects millions worldwide. This insidious disease becomes clinically symptomatic during the sixth decade of life, but there are reasons for believing that the disease process may begin one or two decades earlier, and abnormal metabolism of amyloid abeta peptides may be an important contributing factor.. I have been analyzing naturally occurring auto-antibodies to the amyloid abeta protein as a measure of the bodys response to either elevated levels or abnormal forms of these peptides. It is my feeling that the development of a reliable way to identify individuals who are risk for AD before the disease is evident is a critical unmet need. This lack of early detection hampers our ability to develop new therapies.. Specialized Terms: Pathogenesis of Alzheimers disease; Neurodegeneration; Amyloid abeta metabolism; Auto-antibodies; ...
Researchers have found that a protein variation linked by some genetic studies to Alzheimers disease is consistently present in the brains of people with Alzheimers. In further biochemical and cell culture investigations, they have shown that this protein, known as ubiquilin-1, performs a critical Alzheimers-related function: it chaperones the formation of amyloid precursor protein, a molecule whose malformation has been directly tied to Alzheimers pathology.. What we saw here is that in all 20 of the Alzheimers brains we examined the ubiquilin-1 protein level was lower, and thats completely new, said University of Texas Medical Branch at Galveston assistant professor José Barral, co-author of a paper on the study now online in the Journal of Biological Chemistry. Our experiments looked at the consequences of decreased ubiquilin-1, and showed that its necessary for the proper handling of amyloid precursor protein.. APP has been a major focus of Alzheimers investigators for ...
Brussels, Belgium, 19 July 2017 - Today, the Innovative Medicines Initiative (IMI) is launching two new Calls for proposals with topics on Alzheimers disease, big data, vaccines, autoimmune disease, the blood-brain barrier, drug development, and the exploitation of IMI project results. The total budget for the two Calls stands at just over EUR 130 million. Around half of this comes from the European Commissions Horizon 2020 programme. The other half comes from EFPIA companies as well as IMI Associated Partners.
TY - JOUR. T1 - A novel γ-secretase assay based on detection of the putative C-terminal fragment-γ of amyloid β protein precursor. AU - Pinnix, Inga. AU - Musunuru, Usha. AU - Tun, Han W. AU - Sridharan, Arati. AU - Golde, Todd. AU - Eckman, Christopher. AU - Ziani-Cherif, Chewki. AU - Onstead, Luisa. AU - Sambamurti, Kumar. PY - 2001/1/5. Y1 - 2001/1/5. N2 - Alzheimers disease is characterized by the deposits of the 4-kDa amyloid β peptide (Aβ). The Aβ protein precursor (APP) is cleaved by β-secretase to generate a C-terminal fragment, CTFβ, which in turn is cleaved by γ-secretase to generate Aβ. Alternative cleavage of the APP by α-secretase at Aβ16/17 generates the C-terminal fragment, CTFα. In addition to Aβ, endoproteolytic cleavage of CTFα and CTFβ by γ-secretase should yield a C-terminal fragment of 57-59 residues (CTFγ). However, CTFγ has not yet been reported in either brain or cell lysates, presumably due to its instability in vivo. We detected the in vitro ...
Much of the genetic research on Alzheimers centers on amyloid-beta, a key component of brain plaques that build up in the brains of people with the disease. In the new study, the scientists identified several genes linked to the tau protein, which is found in the tangles that develop in the brain as Alzheimers progresses and patients develop dementia. The findings may help provide targets for a different class of drugs that could be used for treatment.. The researchers reported their findings online April 4 in the journal Neuron.. We measured the tau protein in the cerebrospinal fluid and identified several genes that are related to high levels of tau and also affect risk for Alzheimers disease, said senior investigator Alison M. Goate, DPhil, the Samuel and Mae S. Ludwig Professor of Genetics in Psychiatry. As far as were aware, three of these genes have no effect on amyloid-beta, suggesting that they are operating through a completely different pathway.. A fourth gene in the mix, APOE, ...
TY - JOUR. T1 - Binding of apolipoprotein E inhibits the oligomer growth of amyloid-β peptide in solution as determined by fluorescence cross-correlation spectroscopy. AU - Ly, Sonny. AU - Altman, Robin. AU - Petrlova, Jitka. AU - Lin, Yu. AU - Hilt, Silvia. AU - Huser, Thomas R. AU - Laurence, Ted A.. AU - Voss, John C. PY - 2013/4/26. Y1 - 2013/4/26. N2 - One of the primary neuropathological hallmarks of Alzheimer disease is the presence of extracellular amyloid plaques resulting from the aggregation of amyloid-β (Aβ) peptides. The intrinsic disorder of the Aβ peptide drives self-association and progressive reordering of the conformation in solution, and this dynamic distribution of Aβ complicates biophysical studies. This property poses a challenge for understanding the interaction of Aβ with apolipoprotein E (apoE). ApoE plays a pivotal role in the aggregation and clearance of Aβ peptides in the brain, and the ε4 allele of APOE is the most significant known genetic modulator of ...
Alzheimers disease is the most common cause of dementia. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease--ie, plaques, composed of amyloid beta (Abeta), and tangles, composed of hyperphosphorylated tau. However, as our knowledge increases so does our appreciation for the pathogenic complexity of the disorder. Familial Alzheimers disease is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to Abeta metabolism. By contrast with familial disease, sporadic Alzheimers disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing in concert with a complex interaction of both genetic and environmental risk factors. This seminar reviews the key aspects of the disease, including epidemiology, genetics, ...
TY - JOUR. T1 - Effects of 4-hydroxy-nonenal and amyloid-β on expression and activity of endothelin converting enzyme and insulin degrading enzyme in SH-SY5Y cells. AU - Wang, Rui. AU - Wang, Suqing. AU - Malter, James S.. AU - Wang, Deng Shun. PY - 2009. Y1 - 2009. N2 - The cerebral accumulation of amyloid-β (Aβ) is a consistent feature of and likely contributor to the development of Alzheimers disease (AD). In addition to dysregulated production, increasing experimental evidence suggests reduced catabolism plays an important role in Aβ accumulation. Although endothelin converting enzyme (ECE) and insulin degrading enzyme (IDE) degrade and thus contribute to regulating the steady-state levels of Aβ, how these enzymes are regulated remain poorly understood. In this study, we investigated the effects of 4-hydroxy-nonenal (HNE) and Aβ on the expression and activity of ECE-1 and IDE in human neuroblastoma SH-SY5Y cells. Treatment with HNE or Aβ upregulated ECE-1 mRNA and protein, while IDE ...
The structures of amyloid fibrils and oligomers represent a vast frontier, of yet unknown scope. The fibrils and aggregates that amyloidogenic peptides and proteins form are rich in β-sheets, and their structures are tremendously important in amyloid diseases. Many structures of amyloid fibrils have been discovered by solid-state NMR spectroscopy of amyloidogenic peptides and proteins and by X-ray crystallography of smaller fragments.1-4 Studying amyloid oligomer structures at high resolution is challenging, because amyloid oligomers are heterogeneous and dynamic, forming various species of different sizes and morphologies. Although a few structures of amyloid oligomers have been discovered in the last decade, there are not enough to provide a full understanding of amyloid assemblies.5-7 Our laboratory has pioneered the use of macrocyclic β-sheets as a tool for exploring the structures of amyloid oligomers. In collaboration with the Eisenberg group, we began using X-ray crystallography to ...
The purpose of this work is the reduction in the Abeta amyloid peptide burden in brain of Alzheimers disease (AD) transgenic mice without the concomitant elevation in plasma Abeta amyloid peptide. APPswe,PSEN1dE9 mice were studied at 12 months of age. The mice were shown to have considerable Abeta amyloid plaques in cerebral cortex based on immunocytochemistry. The mice were treated every 3C4 days by intravenous injections of either saline or the cTfRMAb-ScFv fusion protein at an injection dose of 1 1 mg/kg for 12 consecutive weeks. The brain A1C42 concentration was reduced 40% in the fusion protein treated mice, without any elevation in plasma A1C42 concentration. No cerebral micro-hemorrhage was observed in the treated mice. These results display that brain-penetrating antibody pharmaceutics can be developed for mind disorders such as AD TAE684 following a re-engineering of the antibody like a fusion protein that is transferred across the BBB via receptor-mediated transport. Keywords: ...
Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimers disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimers disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.
Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimers disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Abeta42 specifically in adult neurons, to avoid developmental effects. Abeta42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment) rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by removal of
Its often stated as fact that Alzheimers disease is the result of a buildup of beta-amyloid plaques in your brain. Such plaques may increase in your brain as you age, but tend to be far more abundant in people with Alzheimers disease.. Some people have a genetic mutation known to increase the production of beta-amyloid, but in most people the cause behind such buildup is unknown.. Provocative new research suggests that beta-amyloid buildup may not be intrinsically abnormal, and instead, may act as a natural antibiotic that protects your brain from infection. Alzheimers disease, then, might be a byproduct of your brains attempts to fight off infections.. Alzheimers Disease as a Byproduct of Infectious Disease. Harvard researchers have suggested that beta-amyloid proteins are antimicrobial peptides (part of your innate immune response) and have a beneficial role to play in your brain.. If viruses or bacteria cross your blood-brain barrier, the beta-amyloid traps the foreign invader and ...
Title: Non-Steroidal Anti-Inflammatory Drugs as Anti-Amyloidogenic Compounds. VOLUME: 14 ISSUE: 30. Author(s):Mie Hirohata, Kenjiro Ono and Masahito Yamada. Affiliation:Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.. Keywords:Alzheimers disease, amyloid β-peptide (Aβ), amyloidosis, α-synuclein fibrils, central nervous system, neuroinflammation, non-steroidal anti-inflammatory drugs (NSAIDs), protein-misfolding disorders. Abstract: Amyloidosis is a clinical disorder caused by deposition of proteins that abnormally self-assemble into insoluble fibrils and impair organ function. More than 20 unrelated precursor proteins lose their native structure and misfold, leading to the formation of amyloid fibrils. The latter share cross-β core structure in vivo and in vitro and gain abnormal functions. Local amyloid deposition occurs in the central nervous system in Alzheimers disease (AD) and cerebral amyloid ...
Health, ...For decades the amyloid hypothesis has dominated the research field in...The research groups data offers an opposite hypothesis suggesting th...The study published in the October issue of the Journal of Neurosc...Contrary to the dominant theory where aggregated extracellular beta-a...,New,findings,contradict,dominant,theory,in,Alzheimers,disease,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Resveratrol has also been shown to promote the clearance of amyloid-beta peptides. It has also been shown that non-alcoholic ... The study showed that resveratrol found in Cabernet Sauvignon can reduce levels of amyloid beta peptides, which attack brain ... "Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides". J. Biol. Chem. 280 (45): 37377-82. doi:10.1074/ ...
November 2000). "Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer's beta-amyloid peptide, ... August 2002). "Assembling amyloid fibrils from designed structures containing a significant amyloid beta-peptide fragment". The ... The "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built ... Finder VH, Vodopivec I, Nitsch RM, Glockshuber R (February 2010). "The recombinant amyloid-beta peptide Abeta1-42 aggregates ...
"Amyloid-beta as a "difficult sequence" in solid phase peptide synthesis". Protein and Peptide Letters. 11 (4): 377-384. doi: ... Chemical peptide synthesis most commonly starts at the carboxyl end of the peptide (C-terminus), and proceeds toward the amino- ... The crude peptide can be purified using reversed-phase HPLC. The purification process, especially of longer peptides can be ... Microwave-assisted peptide synthesis has been used to complete long peptide sequences with high degrees of yield and low ...
"Alzheimer's disease beta-amyloid peptides are released in association with exosomes". Proceedings of the National Academy of ... "Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting". Science. 320 (5875): 520-523. Bibcode: ...
It also degrades the amyloid beta peptide whose abnormal folding and aggregation in neural tissue has been implicated as a ... Iwata N, Higuchi M, Saido TC (November 2005). "Metabolism of amyloid-beta peptide and Alzheimer's disease". Pharmacol. Ther. ... Because neprilysin is thought to be the rate-limiting step in amyloid beta degradation, it has been considered a potential ... Neprilysin-deficient knockout mice show both Alzheimer's-like behavioral impairment and amyloid-beta deposition in the brain, ...
2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation". Nat. Med. 10 (9): 959-65. doi: ...
Guo Q, Xie J (Feb 2004). "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4". ... Xie J, Guo Q (Jun 2004). "AATF protects neural cells against oxidative damage induced by amyloid beta-peptide". Neurobiology of ... "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4". The Journal of Biological ...
Nelson TJ, Alkon DL (2007). "Protection against beta-amyloid-induced apoptosis by peptides interacting with beta-amyloid". J ... It has been shown to interact with a number of proteins, such as beta-amyloid, protein elongation factor 1alpha, and otoferlin ... Kwok SC, Liu X, Mangel P, Daskal I (2006). "PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer ...
2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation". Nat. Med. 10 (9): 959-65. doi: ...
... which cleaves the amyloid precursor protein to produce the amyloid-beta peptide. These amyloid-beta peptides aggregate together ... Experiments in mice have found that M1 and M3 receptor agonists inhibit the formation of amyloid-beta and target GSK-3B.[ ... M1 receptor activation appears to decreases tau hyperphosphorylation and amyloid-beta accumulation. Sigma1 activation appears ... September 2016). "Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid β-peptide production". Journal ...
This protein may be a target of neurotoxic beta-amyloid peptide, and may mediate cellular vulnerability to beta-amyloid peptide ... Beta-amyloid peptide has been established to be a causative factor in neuron death and the consequent diminution of cognitive ... Lee Y, Chang DJ, Lee YS, Chang KA, Kim H, Yoon JS, Lee S, Suh YH, Kaang BK (2003). "Beta-amyloid peptide binding protein does ... The protein encoded by this gene is a beta-amyloid peptide-binding protein. It contains a structural module related to that of ...
Milner-White, JE; Watson, JD; Qi, G; Hayward, S (September 2006). "Amyloid formation may involve alpha- to beta sheet ... the type I and type II beta turns differ by a simple flip of the central peptide group of the turn. The significance of peptide ... many structures need correction by peptide-plane flips or peptide bond flips. Hayward, S. (2001). "Peptide-plane flipping in ... peptide flips have been described as significant in the catalytic cycle of flavodoxin and in the formation of amyloid ...
Alzheimer's is associated with toxic aggregations of the amyloid beta (Aβ) peptide, caused by Aβ misfolding and clumping ... "Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of ... "Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid". Proc Natl Acad Sci USA. ... "Rationally Designed Turn Promoting Mutation in the AmyloidPeptide Sequence Stabilizes Oligomers in Solution". PLOS ONE. 6 (7 ...
January 2007). "The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell ... "Oxidative stress and the amyloid beta peptide in Alzheimer's disease". Redox Biology. 14: 450-464. doi:10.1016/j.redox.2017.10. ... "Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloidpeptide and τ levels: target engagement, ... significantly lowers brain levels of beta amyloid (1-42)". Alzheimer's & Dementia. 2 (3S_Part_4): S95. doi:10.1016/j.jalz. ...
When Aβ peptide is released by proteolytic cleavage of amyloid-beta precursor protein, some Aβ peptides that are solubilized ... April 2008). "Stabilization of neurotoxic soluble beta-sheet-rich conformations of the Alzheimer's disease amyloid-beta peptide ... will cleave amyloid-beta precursor protein (APP) into various types of amyloid beta (Aβ) protein. Most β-secretase activity ... Amyloid beta (Aβ) is composed of a family of peptides produced by proteolytic cleavage of the type I transmembrane spanning ...
Haass C; Selkoe DJ (2007). "Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide ... amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter ... Findeis MA (November 2007). "The role of amyloid beta peptide 42 in Alzheimer's disease". Pharmacology & Therapeutics. 116 (2 ... 2019). "Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron ...
PDB: 3MOQ​ McCandless, Gregory T. (2008). Synthesis of disubstituted amino acids and peptide inhibitors of amyloid beta ... p3 peptide also known as amyloid β- peptide (Aβ)17-40/42 is the peptide resulting from the b- and γ-secretase cleavage from the ... That is why p3 peptide represents the benign form of amyloid. Energy plays a very important role in p3 peptides. While Aβ ... p3 peptide generates from the 17-40 or 17-42 sequence of the amyloid precursor protein (APP), which is a type I integral ...
Alzheimer's disease is characterized by build-ups of aggregates of the peptide beta-amyloid. Apolipoprotein E enhances ... "Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol". bioRxiv: 2020.06.18.159632. doi:10.1101/ ... high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease". ... Recently, the amyloid hypothesis of Alzheimer's disease has been questioned, and an article in Science claimed that "Just as ...
"Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline". JAMA. 283 (12): 1571-1577. doi ... "Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation". ... In Alzheimer disease, Buxbaum has conducted several cell-biological and patient-based analyses of APP and A-beta and he and his ... that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid ...
When proteins spontaneously aggregate they can form fibrous clumps known as amyloids. Amyloid-beta peptides are associated with ... Linse has demonstrated that the process of nucleation and growth of amyloid-beta peptide occurs in two phases; first the ... Her research makes use of a variety of analytical tools to study protein amyloid formation. In 2020 Linse and co-workers ... "New mathematical model for amyloid formation: Equations describe chemical reactions responsible for the formation of protein ...
He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R (2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide ...
Plaques are made up of small peptides, typically 39-43 amino acids in length, called amyloid beta (also written as A-beta or Aβ ... June 1990). "Cleavage of amyloid beta peptide during constitutive processing of its precursor". Science. 248 (4959): 1122-4. ... amyloid beta: the major component of amyloid plaques in Alzheimer's disease. prion: main component of prion diseases and ... One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into the dense extracellular amyloid ...
Studies of dementia suggest decreased beta-amyloid deposition. Cerebrolysin is not a scheduled drug in the United States. ... Cerebrolysin (developmental code name FPF-1070) is a mixture of enzymatically treated peptides derived from pig brain whose ... "Neurotrophic activities and therapeutic experience with a brain derived peptide preparation". Ageing and Dementia. Journal of ...
Cho S, Hu Y (2007). "Activation of 5-HT4 receptors inhibits secretion of beta-amyloid peptides and increases neuronal survival ...
2005). "Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against beta-amyloid peptide neurotoxicity". ... It is said to aid in detoxification A scorpion venom peptide was found to help with arthritis in vitro. Various fungi are used ... Lee DG, Jung HJ, Woo ER (September 2005). "Antimicrobial property of (+)-lyoniresinol-3alpha-O-beta-D-glucopyranoside isolated ...
2001). "Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain". Journal of Neurochemistry. 76 (1): ... In a mouse model of Alzheimer's disease, DAPT reduces the levels of beta-amyloid. Geling, A.; Steiner, H.; Willem, M.; Bally- ...
Buildup of beta amyloid (Aβ) peptides is shown to cause and/or trigger Alzheimer's disease. Aβ interferes with BDNF-induced ... which encodes a protein that is necessary for the last step of the sequential proteolytic processing of amyloid precursor ...
"The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease". Progress in Neurobiology ... The buildup of Beta Amyloid plaques, a marker highly associated with Alzheimer's disease, generates cell damaging free radicals ... Vitamin A is an essential nutrient for mammals which takes form in either retinol or the provitamin beta-Carotene. It helps ...
"Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation". Scientific ... Bapineuzumab is an antibody to the beta-amyloid (Aβ) plaques that are believed to underlie Alzheimer's disease neuropathology. ... In previous clinical trials for vaccination against human beta amyloid, called AN-1792, patients with Alzheimer's disease using ... Bapineuzumab has been shown to recognise the extreme N-terminal 5 residues of Aβ peptide in a helical conformation (4HIX.pdb) ...
BACE1 is the major beta secretase for the generation of amyloidpeptides in the neurons. Generation of the 40 or 42 amino ... Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1 ... Drugs to block this enzyme (BACE inhibitors) in theory would prevent the buildup of beta-amyloid and (per the Amyloid ... However a single residue mutation in APP reduces the ability of BACE1 to cleave it to produce amyloid-beta and reduces the risk ...
... was first isolated from mouse embryonic kidney in 1997 as a 36 kDa beta-galactoside lectin protein. Human galectin-9 ... The protein has N- and C- terminal carbohydrate-binding domains connected by a link peptide. Multiple alternatively spliced ... proteopathic aggregates such as tau fibrils and amyloids, and signaling pathways inducing lysosomal permeabilization such as ... Wada J, Kanwar YS (February 1997). "Identification and characterization of galectin-9, a novel beta-galactoside-binding ...
... (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to ... The condition is usually associated with amyloid beta. However, there are types involving other amyloid peptides: the " ... are associated with British amyloid (ABri) and Danish amyloid (ADan) respectively. Both peptides are linked to mutations in ... In all cases, it is defined by the deposition of amyloid beta (Aβ) in the leptomeningal and cerebral vessel walls. CAA ...
... beta-2 microglobulin - beta adrenergic receptor - beta sheet - beta-1 adrenergic receptor - beta-2 adrenergic receptor - beta- ... peptide - peptide bond - peptide elongation factor - peptide elongation factor tu - peptide fragment - peptide initiation ... amyloid - anabolism - anaerobic respiration - analytical chemistry - androgen receptor - angiotensin - angiotensin II - ... calcitonin gene-related peptide - calcitonin gene-related peptide receptor - calcitonin receptor - calcitriol receptor - ...
Sumioka A, Imoto S, Martins RN, Kirino Y, Suzuki T (2003). "XB51 isoforms mediate Alzheimer's beta-amyloid peptide production ... Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene. This ... "Entrez Gene: APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like)". Araki Y, Tomita S, Yamaguchi H ... It stabilises APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the ...
... resulting in production of the neurotoxic amyloid beta (Aβ) peptide that accumulates in extracellular locations forming senile ... Insoluble accumulations of β-amyloid peptide in brain regions related to memory and cognition are a defining characteristic of ... "Beta-amyloid toxicity modifier genes and the risk of Alzheimer's disease". American Journal of Neurodegenerative Disease. 1 (2 ... The amyloid precursor protein (APP) is consecutively transported from the ER after its synthesis to the plasma membrane via the ...
A peptide is a short polymer of amino acids linked by peptide bonds. They have the same chemical structure as proteins, except ... The non-proteinogenic amino acid beta-Methylamino-L-alanine (BMAA) is ubiquitously produced by cyanobacteria in marine, ... "Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain". Proceedings of ... In a cyclic peptide, the ends link to form a stable circular chain. In mammals this stability makes them resistant to the ...
... glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum". ... July 2009). "Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic ... allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha ...
The basis of the [PIN+] prion is an amyloid form of Rnq1 arranged in in-register parallel beta sheets, like the amyloid form of ... There was also evidence that the spacing of charged peptides that prevent amyloid formation, such as proline, is important in ... Wickner RB, Dyda F, Tycko R (February 2008). "Amyloid of Rnq1p, the basis of the PIN+ prion, has a parallel in-register beta- ... In [PSI+] yeast cells the Sup35 protein forms filamentous aggregates known as amyloid. The amyloid conformation is self- ...
... and various proteins such as the amino acid 1 to 42 fragment of Amyloid beta, Humanin, and the N-terminally truncated form of ... Nomenclature for the formyl peptide receptor (FPR) family". Pharmacological Reviews. 61 (2): 119-61. doi:10.1124/pr.109.001578 ... formyl peptide receptor-like 1) - FPR2; receptor for Lipoxin A4 and 15-epi-Lipoxin A4 (or AT-LxA4) eicosanoids but also many ... chemerin C-terminal peptide>18R-hydroxy-eicosapentaenoic acid (18R-EPE)>eicosapentaenoic acid (http://www.guidetopharmacology. ...
Frackowiak J, Mazur-Kolecka B, Kaczmarski W, Dickson D (2001). "Deposition of Alzheimer's vascular amyloid-beta is associated ... HADHB encodes a 51.2 kDa protein that is composed of 474 amino acids; 124 peptides have been observed through mass spectrometry ... Trifunctional enzyme subunit beta, mitochondrial (TP-beta) also known as 3-ketoacyl-CoA thiolase, acetyl-CoA acyltransferase, ... This gene encodes the beta subunit of the mitochondrial trifunctional protein, a catalyst of mitochondrial beta-oxidation of ...
The pathology of AD is also associated with accumulation of amyloid beta peptide (Aβ). While a proper concentration of Aβ in ... Brandenberger AW, Tee MK, Jaffe RB (March 1998). "Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ... February 1998). "The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER ... February 1998). "The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER ...
Recent data have also shown that CALHM1 might facilitate the proteolytic degradation of the cerebral amyloid beta peptide, a ... Vingtdeux V, Chandakkar P, Zhao H, Blanc L, Ruiz S, Marambaud P (May 2015). "CALHM1 ion channel elicits amyloid-β clearance by ...
A frameshift mutation in ubiquitin B can result in a truncated peptide missing the C-terminal glycine. This abnormal peptide, ... This compact globular beta-grasp fold is found in ubiquitin, UBLs, and proteins that comprise a ubiquitin-like domain, e.g. the ... Higher levels of ubiquilin in the brain have been shown to decrease malformation of amyloid precursor protein (APP), which ... However, in cases where APC gene is not mutated, mutations are found in the N-terminus of beta-catenin which renders it ...
The three-dimensional structure of the IL-1α contains an open-ended barrel composed entirely of beta-pleated strands. Crystal ... serum amyloid A inducer or hepatocyte-stimulating factor (HSP), catabolin, hemopoetin-1 (H-1), endogenous pyrogen (EP), and ... the resulting peptide is called "mature" form. Calpain, a calcium-activated cysteine protease, associated with the plasma ... interleukin-1 beta, and interleukin-1 receptor antagonist genes". Genomics. 19 (2): 382-4. doi:10.1006/geno.1994.1076. PMID ...
"An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta -sheet structure for amyloid". Proceedings of ... 2008 in recognition of his contributions in unfolding the structure of amyloid fibrils. The award was presented to him at a ...
Similarly, beta strands can also adopt this property with simple alternation of polar and nonpolar residues. Every N+1 side ... The formation of amyloid fibrils, insoluble aggregates of hydrophobic protein can lead to a myriad of diseases including ... In this model, we do not consider the interactions of the peptide backbone as this maintains its stability in non-polar and ... Incidentally, polar residues interact favourably with water, thus the solvent-facing surface of the peptide is usually composed ...
New evidence suggests ApoER2 plays a major role in the regulation of amyloid-β formation in the brain. The amyloidpeptide is ... The presence of amyloid beta (Aβ) protein deposits in neuronal extracellular space is one of the hallmarks of Alzheimer's ... An example of a decrease in expression of LRP8 is when gamma secretase cleaves LRP8 as well as the ligand amyloid precursor ... Lutters BC, Derksen RH, Tekelenburg WL, Lenting PJ, Arnout J, de Groot PG (2003). "Dimers of beta 2-glycoprotein I increase ...
Oppermann UC, Salim S, Tjernberg LO, Terenius L, Jörnvall H (May 1999). "Binding of amyloid beta-peptide to mitochondrial ... "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in ... "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in ... "An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease". Nature. 389 (6652 ...
Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein by 2 proteases, one of which is the ... cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein". Proceedings of the National ... Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease and a frequent complication ... "Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein". Proceedings of the ...
... the synthesis of short peptides with various amino acid sequences the Miller group are studying the self-assembly of Beta ... "The formation of spherulites by amyloid fibrils of bovine insulin". Proceedings of the National Academy of Sciences. 101 (40): ... "Polymers&Peptides Research Group Website". Retrieved 6 April 2019. "Polymers&Peptides Research ... The synthetic peptide hydrogels were so successful that she set up the spin-out company PeptiGelDesign, a group which worked to ...
G-CSF has been shown to reduce inflammation, reduce amyloid beta burden, and reverse cognitive impairment in a mouse model of ... Peptide hormones, Amgen, Cytokines, Drugs acting on the blood and blood forming organs). ... "Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice". ...
Antibodies targeting amyloid beta peptide proteins which have been used during research on Alzheimer's disease. Anti-N-methyl-D ...
Manczak M, Calkins MJ, Reddy PH (July 2011). "Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with ... The aim of the anti-MFN2 peptide is to make MFN2 not functional so it cannot participate in mitochondrial fusion and in the ... In order to inhibit mitochondrial hyperfusion, an anti-MFN2 peptide has to be used, in order to bind to the mitochondria ... This fragmentation is obvious in the pancreatic beta-cells in the Islets of Langerhans and can inhibit mitochondrial quality ...
For example, factor X deficiency may be seen in amyloidosis, where factor X is adsorbed to the amyloid fibrils in the ... Inoue K, Morita T (November 1993). "Identification of O-linked oligosaccharide chains in the activation peptides of blood ... evidence for identification of residue 63 as beta-hydroxyaspartic acid". Biochemistry. 22 (12): 2875-84. doi:10.1021/ ...
... "alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity". ... Hane M, Lowin B, Peitsch M, Becker K, Tschopp J (October 1995). "Interaction of peptides derived from the Fas ligand with the ... "p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha- ... Sotgia F, Lee H, Bedford MT, Petrucci T, Sudol M, Lisanti MP (December 2001). "Tyrosine phosphorylation of beta-dystroglycan at ...
Peptides. 28 (5): 1012-1019. doi:10.1016/j.peptides.2007.02.001. PMC 1986832. PMID 17346852. Casabiell X, Piñeiro V, Tomé MA, ... Greco SJ, Sarkar S, Johnston JM, Tezapsidis N (February 2009). "Leptin regulates tau phosphorylation and amyloid through AMPK ... activator of beta islet cells, and growth factor. In vertebrates, the nervous system consists of two main parts, the central ... calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y. Leptin binds to its receptors in the ...
Primordial genetics: Information transfer in a pre-RNA world based on self-replicating beta-sheet amyloid conformers". Journal ... A different type of nucleic acid, such as peptide nucleic acid, threose nucleic acid or glycol nucleic acid, could have been ... Maury, C. P. (2009). "Self-proagating beta-sheet polypeptide structures as prebiotic informational entities:The amyloid world ... An origin-of-life theory based on self-replicating beta-sheet structures has been put forward by Maury in 2009. The theory ...
2001). "Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death". Diabetes. 50 (1): 77-82. doi:10.2337/ ... 2002). "Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid ... and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions ... The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse ...
The Alzheimers Disease-Associated Amyloid \(\beta\)-Protein Is an Antimicrobial Peptide. Soscia, ... The Alzheimers disease-associated amyloid \(\beta\)-protein is an antimicrobial peptide. PLoS ONE 5(3): e9505.. en_US. ... Background: The amyloid \(\beta\)-protein (A\(\beta\)) is believed to be the key mediator of Alzheimers disease (AD) pathology ... The Alzheimers Disease-Associated Amyloid \(\beta\)-Protein Is an Antimicrobial Peptide. en_US. ...
Structure of segment KLVFFA from the amyloid-beta peptide (Ab, residues 16-21), alternate polymorph I ... Structure of segment KLVFFA from the amyloid-beta peptide (Ab, residues 16-21), alternate polymorph I. *PDB DOI: 10.2210/ ... AMYLOID BETA A4 PROTEIN. A. 6. Homo sapiens. Mutation(s): 0 Gene Names: APP, A4, AD1. ... Molecular Basis for Amyloid-{Beta} Polymorphism.. Colletier, J., Laganowsky, A., Landau, M., Zhao, M., Soriaga, A.B., ...
Purpose: To identify the molecules responsible for amyloid beta-peptide (1-40) (Abeta(1-40)) uptake by the liver, which play a ... Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid beta-peptide by ... Amyloid beta-Peptides / administration & dosage * Amyloid beta-Peptides / chemistry * Amyloid beta-Peptides / metabolism* ...
Apolipoprotein E binds avidly to beta amyloid (A beta) peptide, a major component of senile plaque of Alzheimers disease, in ... A beta(1-28) and A beta(1-40) peptides were incubated in the presence or absence of apoE3, apoE4, or bovine serum albumin for 4 ... Thus apoE3 and apoE4 each interact with beta amyloid peptide to form novel monofibrillar structures, apoE4 more avidly, a ... Apolipoprotein E associates with beta amyloid peptide of Alzheimers disease to form novel monofibrils. Isoform apoE4 ...
Highly toxic amyloid beta (25-35) protein fragment. Achieve your results faster with highly validated, pure and trusted ... Chemical Structure - beta-Amyloid Peptide (25-35) (human), toxic amyloid beta (25-35) protein fragment (ab120480) ... beta-amyloid-peptide-25-35-human-toxic-amyloid-beta-25-35-protein-fragment-ab120480.pdf ... beta-Amyloid Peptide (25-35) (human), toxic amyloid beta (25-35) protein fragment (ab120480). ...
Here, we used conditioned medium obtained from recombinant HEK-A beta PP cells expressing the human amyloid-beta protein ... Characterization of A beta-CM revealed that it contained picomolar amounts of cell-secreted A beta in its soluble form. ... A beta) peptide contributes to impaired synaptic connections and neurodegenerative processes, and as such, represents a primary ... Inhibition of A beta production appeared necessary but insufficient to prevent neurodegenerative effects associated with AD due ...
The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in ... both precludes amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid ... The orphan drug dichloroacetate reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the ... β-secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta-peptides. Over- ...
... together with beta-Amyloid (1-42) are two major C-terminal variants of the beta-Amyloid protein. These beta-Amyloid peptides ... Beta-Amyloid (1-40) together with beta-Amyloid (1-42) are two major C-terminal variants of the beta-Amyloid protein. These beta ... Amyloid peptides undergo post-secretory aggregation and deposition in the Alzheimers disease brain. This peptide is ...
The Amyloid beta peptide (Abeta) of Alzheimers diseases (AD) is closely linked to the progressive cognitive decline associated ... Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimers disease amyloid-beta peptide. ... Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimers disease amyloid-beta peptide. ... peptide ratios. At sub-equimolar Cu2+:peptide molar ratios, Abeta1-42 forms thioflavin-T reactive amyloid; conversely, at supra ...
Ghrelin and certain other catalog peptides. Consistent lots, and fast delivery time. ... Our prices Beta-Amyloid and Ghrelin peptides Request custom peptide quote Ordering Confidentiality Specials ... Peptide technical Handling of peptides Links to biotechnology sites Peptide M.W. calculator Basic information about peptides ... Recognizing that certain peptides are important to multiple researchers, Biopeptide Co., Inc. has arranged to manufacture and ...
ROCK activation increases β-secretase activity and promotes amyloid-beta (Aβ) production; moreover, Aβ further activates ROCK. ... we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load using amyloid-Positron-Emission Tomography ( ... Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid ... amyloid pathology, neuronal injury, and tau pathology, and (iii) cognitive decline over time. ...
... Author. Sanders, Hiromi M.. en_US. ... Amyloid-beta peptide A beta p3-42 affects early aggregation of full-length A beta 1-42. en_US. ... The major amyloid beta (Aβ) peptides found in the brain of familial and late onset Alzheimers disease include the full-length ... Electron microscopy of peptides individually and in mixtures further supported fluorescence data. These results indicate that A ...
amyloid-beta peptide binding alcohol dehydrogenase. *CAMR. *ERAB. *HADH2. *HCD2. *HSD10. *hydroxysteroid (17-beta) ...
Membrane destabilization induced by beta-amyloid peptide 29-42: importance of the amino-terminus. In: Chemistry and Physics of ... Piracetam inhibits the lipid-destabilising effect of the amyloid peptide Abeta C-terminal fragment. In: BBA - Biomembranes, Vol ... First detection of a plasmid-encoded New-Delhi metallo-beta-lactamase-1 (NDM-1) producing Acinetobacter baumannii using whole ... Restoration of susceptibility of methicillin-resistant staphylococcus aureus to beta-lactam antibiotics by acidic pH : role of ...
This is amino acids 10 to 26 fragment of beta-Amyloid peptide. It is capable of forming fibrils. ... Beta-Amyloid (10-26), Human. Home/Beta Amyloid Peptides/Beta-Amyloid (10-26), Human ... Beta-Amyloid (1-42), FAM-labeled, Human. *[Met]-beta-Amyloid (1-42), 5-TAMRA labeled, Human ...
Cholesterol modulates the Interaction of beta amyloid peptide with lipid bilayers. Liming Qiu, Anthony Lewis, John Como, Mark ... Cholesterol modulates the Interaction of beta amyloid peptide with lipid bilayers. In: Biophysical Journal. 2009 ; pp. 4299- ... Cholesterol modulates the Interaction of beta amyloid peptide with lipid bilayers. / Qiu, Liming; Lewis, Anthony; Como, John et ... Dive into the research topics of Cholesterol modulates the Interaction of beta amyloid peptide with lipid bilayers. Together ...
Lehrer S and Lehrer S: Alignment of Alzheimers disease amyloid β‑peptide and klotho. World Acad Sci J 2: 27, 2020 ... Lehrer, S., Rheinstein, P. H.Alignment of Alzheimers disease amyloid β‑peptide and klotho. World Academy of Sciences ... Lehrer, S., Rheinstein, P. H.Alignment of Alzheimers disease amyloid β‑peptide and klotho. World Academy of Sciences ... In 1991, the amyloid hypothesis postulated that beta amyloid (Aβ) accumulation is a key element (1). Aβ was supposed to ...
amyloid beta peptide release. ↑ α-secretase TACE/ADAM17. [69]. SH-SY5Y (Neuroblastoma). 1 µM CA (12 h). ↑ antioxidant defense ... in U373MG astrocytoma cells CA inhibited amyloid β peptide production and release and this was associated, at least partially, ... Carnosic acid attenuates apoptosis induced by amyloid-β 1-42 or 1-43 in SH-SY5Y human neuroblastoma cells. Neurosci. Res. 2015 ... Carnosic acid suppresses the production of amyloid-β 1-42 and 1-43 by inducing an α-secretase TACE/ADAM17 in U373MG human ...
Insulin also regulates levels of the beta amyloid peptide in the CNS.". Intranasal Insulin Improved Daily Function To enhance ... In animal models of AD, PPAR-gamma agonists have been shown to lower beta amyloid peptide levels, reduce plaque deposition, and ... insulin treatment modulated plasma beta amyloid and cortisol levels.. "The intranasal insulin treatment is very exciting, ... although many still debate the role of amyloid.. "The findings in these studies clearly support the growing paradigm shift ...
Tsai, HHG, Lee, JB, Tseng, SS, Pan, XA & Shih, YC 2010, Folding and membrane insertion of amyloid-beta (25-35) peptide and its ... Dive into the research topics of Folding and membrane insertion of amyloid-beta (25-35) peptide and its mutants: Implications ... Folding and membrane insertion of amyloid-beta (25-35) peptide and its mutants: Implications for aggregation and neurotoxicity ... Folding and membrane insertion of amyloid-beta (25-35) peptide and its mutants : Implications for aggregation and neurotoxicity ...
Interactions of amyloid beta (Abeta) peptides with Cu(II) are believed to play a crucial role in the molecular mechanisms of ... We used recombinant amyloid beta peptide 1-40 (Abeta40) to determine the stoichiometry and dissociation constants of Cu(II)- ... A direct determination of the dissociation constant for the Cu(II) complex of amyloid beta 1-40 peptide. ... complex of amyloid beta 1-40 peptide. Chemical research in toxicology, 23 (2). pp. 336-40. ISSN 1520-5010 ...
深入研究「Computer-aided discovery of novel non-peptide inhibitors against amyloid-beta (Aβ) peptide aggregation for treating ... title = "Computer-aided discovery of novel non-peptide inhibitors against amyloid-beta (Aβ) peptide aggregation for treating ... T1 - Computer-aided discovery of novel non-peptide inhibitors against amyloid-beta (Aβ) peptide aggregation for treating ... Computer-aided discovery of novel non-peptide inhibitors against amyloid-beta (Aβ) peptide aggregation for treating Alzheimers ...
Amyloid beta (Aβ), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of ... peptide has been implicated in the pathogenesis of Alzheimers disease. The authors report that overproduction of axonal or ... Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons. Mol. Cell. Neurosci. 33, 274-282 (2006 ... Amyloid beta (Aβ), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of ...
Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimers disease. Ann ... beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem. 1993 Feb 15. 268(5):3021-4 ... Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a ... Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimers disease-associated pathology in ...
Amyloid beta-Peptides. 2. 2022. 3159. 0.030. Why? Proto-Oncogene Proteins c-fyn. 1. 2014. 121. 0.030. Why? ...
Amyloid beta-Peptides. Gray NE, Morré J, Kelley J, Maier CS, Stevens JF, Quinn JF, Soumyanath A. 2014. Caffeoylquinic acids in ... Caffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity.. J Alzheimers Dis. 40(2):359-73. ... Caffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity.. J Alzheimers Dis. 40(2):359-73. ... Caffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity.. J Alzheimers Dis. 40(2):359-73. ...
Decreased levels of amyloid beta peptide in the brains of smokers. In: European Journal of Neurology: 9th Congress of the EFNS ... Preferential deposition of amyloid beta protein (A beta) in the form A beta(40) in Alzheimers disease is associated with a ... Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular ... Decreased levels of amyloid-beta peptide in the entorhinal cortex of normal elderly individuals associated with tobacco smoking ...
102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 29 * 108010090849 Amyloid beta-Peptides Proteins 0.000 ...
... the amyloid precursor protein (APP). According to the amyloid hypothesis cascade, the beta-amyloid (Aβ) peptide deposits are ... Plaques are formed mostly from the deposition of amyloid beta (Ab) a peptide derived from amyloid precursor protein (APP). The ... Amyloid precursor protein-induced axonopathies are independent of amyloid-beta peptides. Hum Mol Genet. 2008, 17: 3474-3486. ... Link CD: Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci USA. 1995, 92: 9368- ...
  • Background: The amyloid \(\beta\)-protein (A\(\beta\)) is believed to be the key mediator of Alzheimer's disease (AD) pathology. (
  • Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. (
  • Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. (
  • Apolipoprotein E binds avidly to beta amyloid (A beta) peptide, a major component of senile plaque of Alzheimer's disease, in an isoform-specific manner. (
  • Thus apoE3 and apoE4 each interact with beta amyloid peptide to form novel monofibrillar structures, apoE4 more avidly, a finding consistent with the biochemical and genetic association between apoE4 and Alzheimer's disease. (
  • Oligomeric amyloid-beta (A beta) peptide contributes to impaired synaptic connections and neurodegenerative processes, and as such, represents a primary therapeutic target for Alzheimer's disease (AD)-modifying approaches. (
  • The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in Alzheimer's disease. (
  • These beta-Amyloid peptides undergo post-secretory aggregation and deposition in the Alzheimer's disease brain. (
  • Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimer's disease amyloid-beta peptide. (
  • The Amyloid beta peptide (Abeta) of Alzheimer's diseases (AD) is closely linked to the progressive cognitive decline associated with the disease. (
  • The major amyloid beta (Aβ) peptides found in the brain of familial and late onset Alzheimer's disease include the full-length Aβ1-42 and N-terminally truncated, pyroglutamylated peptides Aβp3-42 and Aβp11-42. (
  • The mechanisms of interfacial folding and membrane insertion of the Alzheimer's amyloid-β fragment Aβ(25-35) and its less toxic mutant, N27A-Aβ(25-35) and more toxic mutant, M35A-Aβ(25-35), are investigated using replica-exchange molecular dynamics in an implicit water-membrane environment. (
  • Interactions of amyloid beta (Abeta) peptides with Cu(II) are believed to play a crucial role in the molecular mechanisms of neurotoxicity of Alzheimer's disease. (
  • A non-peptide inhibitor that is metabolically stable, orally active and capable of crossing the blood-brain barrier has been a popular option for treating Alzheimer's disease (AD). (
  • The β-amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. (
  • The detection of amyloid-β (Aβ) deposition in the brain provides crucial evidence in the clinical diagnosis of Alzheimer's disease (AD). (
  • Ganesan Narsimhan (right) and Xiao Zhu simulated the effect beta-amyloid peptides have on neural cells, showing what may be the role these substances have in causing brain cell death and some neurodegenerative diseases, such as Alzheimer's disease. (
  • Beta-amyloid peptides, protein fragments that form naturally in the brain and clump into plaques in Alzheimer's disease patients, are thought to be responsible for neuron death, but it hasn't been clear how the substances kill cells. (
  • The findings are the first to show how beta-amyloid forms the pores that kill neural cells in patients afflicted with Alzheimer's disease and suggest targets that could offer new treatments. (
  • Narsimhan focused on Aβ 1-42 since an imbalance in the concentration of this peptide is associated with Alzheimer's cell death. (
  • But the work suggests that neural cell death in Alzheimer's disease could be slowed or stopped with therapies that inhibit formation of these toxic beta-amyloid peptide aggregates. (
  • Some amyloid related proteins/peptides are involved in aggregation and pore formation in phospholipid membranes (cell membranes), which result in a variety of neurological disorders such as Alzheimer's disease, Parkinson's disease and Huntington disease. (
  • In their study, recently published in the journal Science Translational Medicine , Prof. Götz and his colleague Gerhard Leinenga - also of the Clem Jones Centre for Ageing Dementia Research - reveal how the new ultrasound approach removed beta-amyloid plaques from the brains of Alzheimer's mouse models, restoring their memory. (
  • Beta-amyloid is a protein fragment, or peptide, believed to be involved in the development of Alzheimer's. (
  • Though it is unclear exactly how beta-amyloid plaques contribute to Alzheimer's disease , studies have suggested they interfere with communication between nerve cells, making it difficult for them to survive. (
  • In May 2014, for example, Medical News Today reported on a study revealing how a commonly prescribed antidepressant reduced beta-amyloid production in Alzheimer's mouse models. (
  • Our findings suggest that repeated SUS is useful for removing [beta-amyloid] in the mouse brain without causing overt damage, and should be explored further as a noninvasive method with therapeutic potential in Alzheimer's disease. (
  • IHC staining of biotin anti-β-Amyloid, 1-16 antibody (clone 6E10) on formalin-fixed paraffin-embedded human Alzheimer's disease brain tissue. (
  • Alzheimer's disease is characterized by the accumulation of aggregated Aβ peptides in senile plaques and vascular deposits. (
  • The progressive accumulation of extracellular amyloid plaques in the brain is a common hallmark of Alzheimer's disease. (
  • Researchers studying peptides using the Gordon supercomputer at the San Diego Supercomputer Center (SDSC) at the University of California, San Diego (UCSD) have found new ways to elucidate the creation of the toxic oligomers associated with Alzheimer's disease. (
  • Aggregation of misfolded neuronal proteins and peptides may play a primary role in neurodegenerative disorders, including Alzheimer's disease. (
  • However, he noted that within the brains of Alzheimer's patients, the formation of oligomers and fibrils depends on any number of biochemical influences such as peptide concentration, oxidation, neurotoxins, and acidity. (
  • This, as well as previous results, suggests that targeting selected amyloid-beta dimers may be important in an effort to ameliorate the episodic memory described in mild cognitive impairment and the early stages of Alzheimer's disease," said Masliah. (
  • The new study shows that once the bacteria are in the central nervous system, the cells of the brain react within days by depositing beta amyloid peptide, the hallmark plaque of Alzheimer's disease. (
  • As per studies suggest plaque of the amyloid peptides are found in the brain of Alzheimer's patient. (
  • Thus, a growing number of clinical trials and research activity to develop treatment and drugs for Alzheimer's are fueling the growth of the Global Amyloid Peptides Market. (
  • Amyloid beta is large membrane protein which plays essential role in neural growth and repair but in later stage, the corrupted form can destroy nerve cells and cause loss of thoughts and memory that may lead to Alzheimer's disease. (
  • 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 ). (
  • Radius Health claims that the SARM blocks the impact and suppresses the production of amyloid-beta proteins that are oftentimes associated with the onset of Alzheimer's disease. (
  • These neurotoxic peptides are generated from the amyloid precursor protein via sequential cleavage by β- and γ-secretases in the 'amyloidogenic' proteolytic pathway. (
  • Alternatively, the amyloid precursor protein can be processed via the 'non-amyloidogenic' pathway which, through the action of the α-secretase a disintegrin and metalloproteinase (ADAM) 10, both precludes amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid precursor protein fragment, sAPPα. (
  • In the current study, we investigated whether the orphan drug, dichloroacetate, could alter amyloid precursor protein proteolysis. (
  • In SH-SY5Y neuroblastoma cells, dichloroacetate enhanced sAPPα generation whilst inhibiting β-secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta-peptides. (
  • Over-expression of the amyloid precursor protein partly ablated the effect of dichloroacetate on amyloidogenic and non-amyloidogenic processing whilst over-expression of the β-secretase only ablated the effect on amyloidogenic processing. (
  • Similar enhancement of ADAM-mediated amyloid precursor protein processing by dichloroacetate was observed in unrelated cell lines and the effect was not exclusive to the amyloid precursor protein as an ADAM substrate, as indicated by dichloroacetate-enhanced proteolysis of the Notch ligand, Jagged1. (
  • Despite altering proteolysis of the amyloid precursor protein, dichloroacetate did not significantly affect the expression/activity of α-, β- or γ-secretases. (
  • In conclusion, dichloroacetate can inhibit amyloidogenic and promote non-amyloidogenic proteolysis of the amyloid precursor protein. (
  • The main constituent of the amyloid deposits is an amphiphilic peptide, derived by proteolysis from a large membrane spanning precursor protein, the amyloid precursor protein (APP). (
  • Plaques are formed mostly from the deposition of amyloid beta (Ab) a peptide derived from amyloid precursor protein (APP). (
  • Aβ peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by β-secretases and γ-secretases generating diverse Aβ species. (
  • Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia. (
  • Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor protein. (
  • All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (
  • The disease process is associated with β-amyloid (Aβ) plaques, tau neurofibrillary tangles and neuroinflammation. (
  • The morphologic features observed in AD patients at autopsy include both extracellular amyloid deposits as amyloid senile plaques and intracellular neurofibrillary tangles (NFT). (
  • These characteristics or hallmarks of AD include the formation of B -amyloid (A B ) plaques and neurofibrillary tangles (NFTs), and the development of mitochondrial dysfunction and autophagy dysfunction. (
  • AD is characterized by accumulation of the β-amyloid peptide (amyloid plaques) and neurofibrillary tangles of hyperphosphorylated tau protein within the brain. (
  • Cu2+ ions can induce the de novo aggregation of the Abeta peptide into non-amyloidogenic aggregates and the production of a toxic species. (
  • Here we demonstrate that the aggregation state of Abeta1-42 at neutral pH is governed by the Cu2+:peptide molar ratio. (
  • By probing amyloid content and total aggregation, we observed a distinct Cu2+ switching effect centered at equimolar Cu2+:peptide ratios. (
  • We investigated the aggregation kinetics of brainspecific Aβ peptides to better understand their potential roles in plaque formation. (
  • The intermolecular aggregation, prompted by instability, strongly correlates to the increase of ordered structures rich of beta-sheets, typical of amyloid assemblies. (
  • This is amino acids 10 to 26 fragment of beta-Amyloid peptide. (
  • In 1991, the amyloid hypothesis postulated that β‑amyloid (Aβ) accumulation is a key element. (
  • Additionally, neuronal infection with HSV-1 triggers the accumulation of amyloid beta deposits and hyperphosphorylated tau, and results in oxidative stress and synaptic dysfunction. (
  • A B plaques are caused by the accumulation of amyloid-beta peptides. (
  • Earlier this month, MNT reported on a study published in the journal Brain , in which researchers identified beta-amyloid accumulation in the brains of adults as young as 20 years old . (
  • To identify the molecules responsible for amyloid beta-peptide (1-40) (Abeta(1-40)) uptake by the liver, which play a major role in the systemic clearance of Abeta(1-40). (
  • Importantly, the formation of dityrosine crosslinked Abeta, by the oxidative modification of the peptide, only occurs at equimolar molar ratios and above. (
  • The differences between this and other determinations of this constant and its relevance for the understanding of Cu(II) interaction with Abeta peptides are discussed. (
  • Some clinical isolates have been observed to shield themselves with extracellular amyloid fibers called curli at physiologic temperature. (
  • Curli fibers are extracellular amyloid fibrils that are variably expressed by E. coli (for review, see [1] ). (
  • However, the lack of efficacy of drugs that inhibit production of A beta demonstrates the need for a better characterization of its toxic effects, both on synaptic and neuronal function. (
  • Here, we investigate whether non-cholesterol sterols and oxysterols in the central nervous system are associated with (i) the presence of cerebral AD pathology, (ii) distinct aspects of AD pathology, i.e. amyloid pathology, neuronal injury, and tau pathology, and (iii) cognitive decline over time. (
  • This antibody is reactive to amino acid residue 1-16 of beta amyloid. (
  • This rat monoclonal antibody was raised against synthetic monomeric human Amyloid-beta peptide and is specific for human Amyloid beta. (
  • Single beta-amyloid peptides, after misfolding, can aggregate and form fibrils and successively plaques. (
  • These results indicate that Aβ-Aβ peptide interactions involving different forms may play a critical role in senile plaque formation and maintenance of the soluble Aβ pool in the brain. (
  • Since proteins and peptides are normal constituents of all foods, that work holds promise for creating "green" food safety products, such as sprays for fresh produce and packaging films. (
  • In another study, which appeared in Neurochemistry International , researchers reported that S. miltiorrhiza extracts can protect neurons from B -amyloid protein-induced cell death. (
  • Some forms of the aggregated peptides are toxic to neurons. (
  • Nicergoline has shown to protect cultured neurons against β-amyloid toxicity. (
  • Nicergoline is a drug used for age-dependent cognitive impairment and it protects cultured neurons against β-amyloid toxicity. (
  • Aβ(25-35) and N27A-Aβ(25-35) peptides share similar mechanisms: the peptides are first located in the membrane hydrophilic region where their C-terminal residues form helical structures. (
  • The peptides attempt to insert themselves into the membrane hydrophobic region using the C-terminal or central hydrophobic residues. (
  • A small portion of peptides can successfully enter the membrane's hydrophobic core, led by their C-terminal residues, through the formation of continuous helical structures. (
  • The three studied peptides share a similar helical structure for their C-terminal five residues, and these residues mainly buried within the membrane's hydrophobic region. (
  • That synthetic peptides corresponding to PrP residues 109-141 can reproduce some of the properties of PrP Sc in vitro is well known. (
  • In this procedure, the hydrophobic residues of the valine at place 6 of the beta concatenation of HbS associates with the hydrophobic spot, doing the hemoglobin molecules to aggregate and organize hempen precipitates. (
  • Understanding the mechanisms of Aβ peptide interfacial folding and membrane insertion will provide new insights into the mechanisms of neurodegradation and may give structurebased clues for rational drug design preventing amyloid associated diseases. (
  • In collaboration with Xiao Zhu , a senior research scientist for Information Technology at Purdue Research Computing, Narsimhan's research group performed computer simulations showing that a single Aβ 1-42 peptide had no effect on neural cells, but in groups of three or five, called oligomers, they are able to penetrate the cell membrane and form small pores and kill the neural cells. (
  • In this research, the mechanism of pore formation by β amyloid (Aβ) peptides was investigated using molecular dynamics simulation by simulating the interaction of the Aβ (11-42) peptide, with a lipid membrane and the potential of the mean force of interaction was evaluated. (
  • The results indicated that Aβ (11-42) peptide oligomers with peptide numbers larger than two were more likely to lead to lipid deformation and water channels, and the free energy of penetration into the membrane decreased with the increasing number of peptides. (
  • The researchers investigated the single and dimer forms of the peptide with a combination of computational methods including molecular dynamics, molecular docking, molecular interactions with the membrane, as well as mutagenesis, biochemical, and electron microscopy studies. (
  • Amyloid is the large membrane protein which plays vital role in neural growth. (
  • Peptides are synthesized on a coated cellulose membrane that is used as solid phase. (
  • After synthesis peptides can remain on the membrane for an easy and inexpensive peptide array (PepSpots) or be separated from the mebrane and used as individual peptides (PepTrack Fast Track), pooled (SpotMix) or used to print on glass slides (PepStar). (
  • As we age, fragments of beta-amyloid can clump together in the brain, forming plaques that accumulate in the spaces between nerve cells, called synapses. (
  • According to the amyloid hypothesis cascade, the beta-amyloid (Aβ) peptide deposits are the fundamental cause of the disease [ 1 ]. (
  • Forms of Amyloid beta phosphorylated at serine residue 8 have increased propensity to form toxic aggregates as compared to non-phosphorylated species. (
  • Understanding the structure of amyloid-beta dimers might be important for the design of small molecules that block formation of toxic oligomers. (
  • The mechanism by which Cu2+ mediates the change from amyloid material toward Cu2+ induced aggregates is poorly defined. (
  • conversely, at supra-equimolar Cu2+:peptide molar ratios, Abeta1-42 forms both small spherical oligomers approximately 10-20 nm in size and large amorphous aggregates. (
  • He's found that these antimicrobial peptides form aggregates and bore into the cells of foodborne pathogens, creating pores that allow intracellular fluid to leak, thereby, killing the cells and alleviating the threat of food poisoning. (
  • Narsimhan knew that antimicrobial peptides had to form small clusters in order to kill pathogenic cells, and he noticed that while beta-amyloid alone does not cause cell death, formation of beta-amyloid aggregates could. (
  • Synthetic peptides were analyzed individually and in mixtures representing various ratios found in the brain. (
  • A synthetic form of exendin-4, a 39-amino acid peptide isolated from the venom of the Gila monster lizard (Heloderma suspectum). (
  • Amyloid peptides have gained popularity in the Alzheimer disease research project and growing number of Alzheimer cases and also, Amyloid Peptides have been implicated in cancer development has boosted the growth of the Amyloid Peptides Market. (
  • Nevertheless, huge scope for advancement and development in the drug molecule and growing number of disorders such as amyloidosis and Alzheimer are expected to generate lucrative opportunities for Global Amyloid Peptides Market over the forecasted period. (
  • La forma fibrilar amiloide de estos péptidos es el principal componente de las placas amiloides que se encuentran en personas con la enfermedad de Alzheimer y en personas mayores con trisomía 21 (SÍNDROME DE DOWN). (
  • High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. (
  • Brookmeyer, R et al,2007).Alzheimer 's disease is a type of a protein misfolding disease, caused by accretion of abnormally folded amyloid-beta and tau proteins in the encephalon. (
  • GenScript is proud to provide a comprehensive collection of amino acid derivatives , beta-amyloid peptides , blocking peptides , cosmetic peptides , biochemical reagents and pharmaceuticals to clients in cosmetic, pharmaceutical, academic and industry institutions all over the world. (
  • The epitope lies within amino acids 3-8 of beta amyloid (EFRHDS). (
  • Acetylation dictates the morphology of nanophase biosilica precipitated by a 14-amino acid leucine-lysine peptide. (
  • A comparison of the spatial patterns of β-amyloid (Aβ) deposits in five neurodegenerative disorders. (
  • Ubiquitous in all life forms and central to any research or development program involving biomolecules, the interactions between proteins, nucleic acids, peptides and other biomacromolecules lie at the heart of biology, physiology, and medicine. (
  • The metabolic processing of APP that results in Ab formation requires two enzymatic cleavage events, a b-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE) and a g-secretase cleavage dependent on presenilin. (
  • There's more to learn including the synergistic interaction of the peptide bioregulators themselves and if individuals are using hormones concurrently, then there may well be a need to monitor their blood levels more closely with a view to lowering those doses and applications etc. (
  • The interaction with gold suppresses fiber-like conformations of the amyloid beta (16-22) peptide. (
  • Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue A\(\beta\) levels. (
  • Consistent with A\(\beta\)-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-A\(\beta\) antibodies. (
  • As neurodegeneration advances in an older individual, perhaps caused by neuroinflammation related to herpes simplex virus type 1, increasing amounts of amyloid are produced, forming an adhesive web, as the brain tries to hold the pathologic process in check. (
  • The Effect of Beta Amyloid Peptide 1 42 Injection on Oxidative Damage and Apoptosis in Young Adult and Aged Rat Brain. (
  • Simulations of other beta-amyloid peptides and experiments are necessary to confirm the significance of these findings in the brain. (
  • A number of studies have investigated the use of drugs to combat beta-amyloid build-up in the brain. (
  • The ultrasound waves oscillate tremendously quickly, activating microglial cells that digest and remove the amyloid plaques that destroy brain synapses," explains Prof. Götz. (
  • The scientists surveyed all the possible ways to look at the dynamics of conformational changes of these peptides and the possibility that they might organize into the oligomers theorized to be responsible for the degenerative brain disease . (
  • The aim was to evaluate and compare the possible effects of perindopril, and candesartan on cognitive impairment, oxidative stress markers, and brain concentrations of amyloid beta-peptide (Aβ-P) in a rat model of induced dementia. (
  • The commonly performed studies in routine clinical practice are 99m Tc-labeled brain perfusion radiotracers for SPECT imaging and 18 F-FDG and 18 F-labeled β-amyloid imaging radiotracers for PET imaging ( 2 ). (
  • Experiments used established in vitro assays to compare antimicrobial activities of A\(\beta\) and LL-37, an archetypical human AMP. (
  • Monofibrils appeared earlier in apoE4/A beta than in apoE3/A beta in time-course experiments. (
  • The in silico experiments allowed the single amyloid-beta monomers to associate randomly, according to Masliah. (
  • It is suggested that oxidative stress, stress in the Golgi Apparatus, reduction in expression of the set of genes involved in the signaling pathway Epithelial Growth Factor Receptor (EGFR) and in the pathway of the metabolism of beta-amyloid peptide and alteration of the catalytic activity of D2 with consequent changes in serum levels of T3 and T4 may contribute to the development or as aggravating of these conditions. (
  • Unlike purely monofibrillar apoE4/A beta coincubates, apoE3/A beta coincubates also contained double- and triple-stranded structures. (
  • They then looked at how those dimers interacted with additional peptides and which larger structures resulted. (
  • We observed that soluble SDS-stable complexes of apoE3 or apoE4, formed by coincubation with A beta peptide, precipitated after several days of incubation at 37 degrees C with apoE4 complexes precipitating more rapidly than apoE3 complexes. (
  • The formation of intracellular amyloid-like inclusions by mutant proteins is a feature of two groups of codon reiteration diseases, for which there are currently no treatments. (
  • Intracellular amyloid-like inclusions formed by mutant proteins result from polyglutamine expansions in Huntington's disease (HD) and polyalanine expansions in polyadenine binding protein 2 (PABP2) in oculopharyngeal muscular dystrophy (OPMD). (
  • [ 138 , 139 , 140 ] The author's studies determined the ability of these various candidate beta-sheet breaker peptides to inhibit amyloidlike fibril formation of PrP109-141 using a fluorometric assay based on the fluorescence emission of thioflavine T. (
  • This automated process results in the production of huge numbers of peptides making this a fast and economical alternative to other methods that aim for deep T- and B-cell epitope discovery, MS-based proteomics relying on heavy & light reference peptides, antigen target identification and others. (
  • Recognizing that certain peptides are important to multiple researchers, Biopeptide Co., Inc. has arranged to manufacture and keep in stock large quantities of the peptides you see on this page. (
  • Tsigelny also noted that recent improvements in computational processing speed have allowed him and other researchers to use a variety of tools, including computer simulations, to take new approaches to examining amyloid-beta, which has proven too unstable for traditional approaches such as x-ray crystallography. (
  • According to the researchers, their work implicates a more dynamic role for the amyloid-beta dimers than previously thought. (
  • Calcium-Induced Molecular Rearrangement of Peptide Folds Enables Biomineralization of Vaterite Calcium Carbonate. (
  • Characteristic of amyloids, curli fibers are highly stable, insoluble, high molecular weight protein complexes dominated by a beta sheet secondary structure. (
  • Caffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity. (
  • Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. (
  • All the sources of these Peptide Bioregulators are from carefully chosen Danish bovine tissues and processed through pharmaceutical processes and filters. (
  • Pterostilbene attenuates amyloid-ß induced neurotoxicity with regulating PDE4A-CREB-BDNF pathway. (
  • Methodology/Principal Findings: Here, we provide data supporting an in vivo function for A\(\beta\) as an antimicrobial peptide (AMP). (
  • Findings reveal that A\(\beta\) exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. (
  • Ganesan Narsimhan , professor in the Department of Agricultural and Biological Engineering , uses simulations to understand how antimicrobial peptides produced by insects protect them against harmful microorganisms. (
  • that is activated by several ligands including HMGB1 but also by advanced glycation end products (AGEs), S100 proteins, and amyloid β-peptide (Aβ). (
  • Now their published research is in the open and it identifies that each organ / gland / tissue uses a highly specific short chain peptide to act as a 'short cut' to initiate protein synthesis. (
  • The SPOT peptide synthesis technique is an ultra-high-throughput synthesis method for hundreds to thousands of peptides in parallel. (
  • Amyloids are historically associated with the disease, which have recently been recognized as biological structure as life-inspired assemblies. (
  • Remarkably, we showed a greater diversity in amyloid-beta dimers than previously described," said Eliezer Masliah, professor of pathology and medicine at UC San Diego, and a member of the research team. (
  • As previously described for amyloid-beta, the tauopathy phenotype in human myocardium is of diastolic dysfunction. (
  • Single amyloid-beta monomers can pair up to form a variety of dimers that can aggregate into larger peptide rings that reside on cell membranes such as those pictured. (