Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Insulysin: An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC 3.4.24.56.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Serum Amyloid A Protein: An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.Presenilin-1: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Apolipoprotein E3: 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.Neurons: 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.Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Presenilin-2: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Apolipoprotein E4: A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.Neprilysin: 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.Cerebral Amyloid Angiopathy: A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)Synaptophysin: 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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.tau Proteins: Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.ThiazolesAmyloidosis: 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.Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.Islet Amyloid Polypeptide: A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Astrocytes: 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.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Neuroprotective Agents: 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.Amyloid Neuropathies: Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Kinetics: The rate dynamics in chemical or physical systems.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Transfection: 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.Serum Amyloid P-Component: Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Mice, Inbred C57BLCongo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.Peptide Library: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Copper: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Interleukin-1beta: 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.beta 2-Microglobulin: An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Antimicrobial Cationic Peptides: 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.Reactive Oxygen Species: 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, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Oligopeptides: Peptides composed of between two and twelve amino acids.Peptides, Cyclic: 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).Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Models, Biological: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Peptide Mapping: 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.Structure-Activity Relationship: 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.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Alzheimer Vaccines: Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.CHO Cells: 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.Amyloid Neuropathies, Familial: Inherited disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. The different clinical types based on symptoms correspond to the presence of a variety of mutations in several different proteins including transthyretin (PREALBUMIN); APOLIPOPROTEIN A-I; and GELSOLIN.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Receptors, Formyl Peptide: 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.Integrin beta3: 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.Hydrogen-Ion Concentration: 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)Receptors, Adrenergic, beta: 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.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Blotting, Western: 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, Messenger: 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.Natriuretic Peptide, Brain: 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.Bacteriocins: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Microscopy, Atomic Force: A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.Protein PrecursorsSignal Transduction: 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.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Cell Survival: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Apoptosis: 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.Vasoactive Intestinal Peptide: 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: 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.Transforming Growth Factor beta: 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.Cloning, Molecular: 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.Prions: Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization: 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.Gene Expression Regulation: 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.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cell-Penetrating Peptides: Peptides that have the ability to enter cells by crossing the plasma membrane directly, or through uptake by the endocytotic pathway.Peptide Biosynthesis: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Mice, Knockout: 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.Hydrophobic and Hydrophilic Interactions: The thermodynamic interaction between a substance and WATER.Magnetic Resonance Spectroscopy: 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).Molecular Weight: The sum of the weight of all the atoms in a molecule.Nerve Tissue ProteinsEpitopes: Sites on an antigen that interact with specific antibodies.Recombinant Fusion Proteins: 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.Peptide YY: A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion.Rats, Sprague-Dawley: 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, Monoclonal: Antibodies produced by a single clone of cells.Peptide Nucleic Acids: 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.Cricetulus: 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.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Nerve Degeneration: 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.Natriuretic Peptide, C-Type: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Presenilins: Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Maze Learning: Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)Natriuretic Peptides: 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).Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Glycogen Synthase Kinase 3: 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.Memory Disorders: 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.Immunoblotting: 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.Cattle: 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.Receptors, Islet Amyloid Polypeptide: G-protein coupled receptors that are formed through the dimerization of the CALCITONIN RECEPTOR with a RECEPTOR ACTIVITY-MODIFYING PROTEIN. Their affinity for ISLET AMYLOID POLYPEPTIDE is dependent upon which of several receptor activity-modifying protein subtypes they are bound to.Receptors, Peptide: Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.Cerebral Amyloid Angiopathy, Familial: A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.Amino Acids: 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.Spectroscopy, Fourier Transform Infrared: A spectroscopic technique in which a range of wavelengths is presented simultaneously with an interferometer and the spectrum is mathematically derived from the pattern thus obtained.Integrin alpha5beta1: 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.Protein Transport: 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.Enzyme Activation: 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.Integrin beta4: 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.Gastrin-Releasing Peptide: 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.Tumor Cells, Cultured: 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.Neurofibrils: The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.Trypsin: 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 3.4.21.4.Smilacaceae: A plant family of the order Liliales, subclass Liliidae, class Liliopsida (monocotyledon).Peptide PHI: 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.Up-Regulation: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Amino Acid Motifs: 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.Peptide Synthases: Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.Kaempferols: A group of FLAVONOLS based on kaempferol. They are derived from naringenin and can be hydroxylated to QUERCETIN or reduced to leucopelargonidin.Atrial Natriuretic Factor: 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: 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.beta 2-Glycoprotein I: 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.Integrin alpha6beta4: 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.Antibodies: 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).Proteolysis: 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.Neurotoxins: 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.Moraceae: The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.Escherichia coli: 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: 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.Integrins: 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.DNA: 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).Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Molecular Structure: 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.Interleukin-1: 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.Proteins: 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.Calcium: 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.Microscopy, Confocal: 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.Integrin alpha2beta1: 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, Fluorescence: 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.Binding, Competitive: 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.Intracellular Signaling Peptides and Proteins: 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.Neuroblastoma: 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)Immunoprecipitation: 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.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Biological Markers: 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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Receptors, Adrenergic, beta-2: 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.DNA Primers: 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.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Reverse Transcriptase Polymerase Chain Reaction: 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.Amyloidosis, Familial: Diseases in which there is a familial pattern of AMYLOIDOSIS.Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Cell Adhesion: Adherence of cells to surfaces or to other cells.

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)

*Amyloid beta

Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ... Amyloid beta can be measured semiquantitatively with immunostaining, which also allows one to determine location. Amyloid beta ... By NMR-guided simulations, amyloid beta 1-40 and amyloid beta 1-42 also seem to feature highly different conformational states ... Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are crucially involved in Alzheimer's disease as the main ...

*Amyloid precursor protein

"An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease". Nature. 389 (6652 ... a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition". The ... Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause ... Cleavage by gamma secretase within the membrane-spanning domain after beta-secretase cleavage generates the amyloid-beta ...

*Alzheimer's disease research

It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide. Negative results ... The most widely used biomarker is the peptide beta-amyloid 1-42 (Aβ42), which is measured in cerebrospinal fluid. Levels of A ... Gamma secretase is a protein complex thought to be a fundamental building block in the development of the amyloid beta peptide ... One approach is to reduce amyloid beta, for example with bapineuzumab, an antibody in phase III studies for patients in mild to ...

*Neprilysin

It also degrades the amyloid beta peptide whose abnormal misfolding 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. ... Hama E, Saido TC (2005). "Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide". Med. ... Because neprilysin is thought to be the rate-limiting step in amyloid beta degradation, it has been considered a potential ...

*Cabernet Sauvignon

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/ ...

*RTN1

He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R (2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide ...

*RTN3

2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation". Nat. Med. 10 (9): 959-65. doi: ...

*Apoptosis-antagonizing transcription factor

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 ...

*ANAVEX2-73

... 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 ... "Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid β-peptide production". J Cell Mol Med. 20: 1686- ...

*HSD17B10

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 ...

*P3 peptide

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 α- 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 ...

*Joseph Buxbaum

"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 ...

*Estrogen receptor beta

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 (1998). "Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ... and beta (ER-beta) mRNA in the midgestational human fetus". J. Clin. Endocrinol. Metab. 82 (10): 3509-12. doi:10.1210/jc.82.10. ... "The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and ...

*PLCD1

2003). "Amyloid beta peptide (Abeta42) activates PLC-delta1 promoter through the NF-kappaB binding site". Biochem. Biophys. Res ... Guo Y, Philip F, Scarlata S (2003). "The Pleckstrin homology domains of phospholipases C-beta and -delta confer activation ... Keshamouni VG, Mattingly RR, Reddy KB (2002). "Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells ...

*PSEN1

Phiel CJ, Wilson CA, Lee VM, Klein PS (May 2003). "GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides ... A 5-fold drop of amyloid peptide was observed, suggesting that deficiency of presenilin-1 can down regulate amyloid and ... from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease. ... These disease-linked mutations result in increased production of the longer form of amyloid beta (main component of amyloid ...

*NAD(P)H dehydrogenase (quinone 1)

"The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease". Progress in Neurobiology ... Dong GZ, Oh ET, Lee H, Park MT, Song CW, Park HJ (May 2010). "Beta-lapachone suppresses radiation-induced activation of nuclear ...

*PAWR

Guo Q, Xie J, Chang X, Du H (May 2001). "Prostate apoptosis response-4 enhances secretion of amyloid beta peptide 1-42 in human ... Guo Q, Xie J (Feb 2004). "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4". ...

*SYNPR

2004). "Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid beta-peptide-induced cholinergic ...

*Bapineuzumab

"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) ...

*Peroxidase

Atamna H, Boyle K (Feb 2006). "Amyloid-beta peptide binds with heme to form a peroxidase: relationship to the cytopathologies ... Amyloid beta, when bound to heme, has been shown to have peroxidase activity. A typical group of peroxidases are the ...

*Prevention of dementia

Alzheimer's disease causes inflammation in the neurons by its deposits of amyloid beta peptides and neurofibrillary tangles. ... Insulin in the bloodstream is a trigger of amyloid beta-production, so decreased insulin levels decrease the level of amyloid ... It has been theorized that a vaccine could activate the body's own immune system to combat the beta amyloid plaques in ... Lack of sleep may also increase risk of dementia by increasing beta-amyloid deposition. Being neurotic increases the risk of ...

*Common degu

2004), "Human-like rodent amyloid-beta-peptide determines Alzheimer pathology in aged wild-type Octodon degus", Neurobiol. ... "Cloning of complementary DNA's encoding islet amyloid polypeptide, insulin, and glucagon precursors from a New World rodent, ...

*Collagen, type XXV, alpha 1

2005). "CLAC binds to amyloid beta peptides through the positively charged amino acid cluster within the collagenous domain 1 ... 2005). "Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide- ... 2005). "Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into protease resistant aggregates". FEBS J. ... or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits". Am. J. Pathol. 165 ...

*Sulfatide

Han, x. (2010). "The Pathogenic Implication of Abnormal Interaction Between Apolipoprotein E Isoforms, Amyloid-beta Peptides, ... Amyloidpeptide clearance is important so that this accumulation does not occur. Sulfatide facilitates amyloidpeptide ... Sulfatide is also involved in the clearance of amyloidpeptide. Amyloidpeptides are one of the hallmarks of Alzheimer's ... When they are not degraded properly, these peptides accumulate and create plaques, which are clumps of amyloidpeptide pieces ...

*TREM2

... interacts with DAP12 in microglia to trigger phagocytosis of amyloid beta peptide and apoptotic neurons without ...

*Ramakrishnan Nagaraj

"Organic solvent mediated self-association of an amyloid forming peptide from beta(2)-microglobulin: An atomic force microscopy ... He has done considerable work on signal peptides and peptide antibiotics and their structure-function relationships. He is ... Sowmya, B. L., Jagannadham, M. V., and Nagaraj, R. (2006). "Interaction of synthetic peptides corresponding to the scaffolding ... CS1 maint: Multiple names: authors list (link) Pallavi, B.; Nagaraj, R. (2003). "Palmitoylated peptides from the cysteine- rich ...

*Biochemistry of Alzheimer's disease

Amyloid-beta, also written Aβ, is a short peptide that is a proteolytic byproduct of the transmembrane protein amyloid ... Amyloid beta, also written Aβ, is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein ... due to the accumulation of abnormally folded Amyloid-beta proteins in the brains of AD patients. Abnormal amyloid-beta ... 2005). "Globular amyloid beta-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease". J. ...
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 ...
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
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 ...
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 ...
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 ...
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 ...
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:Mouse
Clone: 4G8
Isotype: IgG2b
Reactivity: Human, Mouse
Immunogen: 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/mL
Formulation:PBS (no preservatives); The Ab was purified on Protein G
Applications:The Ab is effective in immunoblotting (WB),
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].
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 ...
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 ...
Amyloid beta peptide, computer illustration. This protein is the primary component of amyloid plagues in the brains of Alzheimers patients. - Stock Image F012/9129
Specifically, they taught adult rats to be afraid of entering a dark chamber. But after intracerebral injections of the Abeta extracts, the rats forgot that they should avoid entering the chamber. The memory impairment was transient. Animals that received injections of extracts depleted of soluble Abeta proteins had no deficit in memory.. In addition to aged normal brain tissue, they also conducted the same studies with tissue from patients diagnosed with other forms of dementia and did not find any synaptic deficits. The investigators also found that injections of Abeta antibodies protected against this memory block, suggesting that Abeta is the rogue protein in the AD brain extracts involved in altering memory.. To address how this happens, the scientists set out to analyze various assembly forms of Abeta in the human brain extracts. They found that single Abeta molecules (monomers) did not harm neuronal synapses. But when a monomer teamed up with another monomer to form a dimer, it apparently ...
In this study, we examined Abca1 gene dose effect on the phenotype of APP transgenic mice expressing human ApoE3 or ApoE4 isoforms. Surprisingly, our results demonstrate that the lack of one copy of Abca1 significantly aggravates memory deficits and amyloid pathology in APP/E4 but not in APP/E3 mice. An important finding of the study was that Aβ clearance from the brain was decreased by Abca1 deficiency in APP/E4/Abca1−/+ but not in APP/E3/Abca1−/+ mice. In contrast, Abca1 deficiency did not affect cognition, amyloid phenotype, and Aβ clearance in APP mice expressing ApoE3. Interestingly, the correlation between plasma HDL and brain amyloid load (Fig. 7) suggests that there may be a causative connection between peripheral lipoproteins and Aβ load in the CNS.. Previous studies demonstrated that ABCA1 affects amyloid deposition and memory deficits in experimental animals (Hirsch-Reinshagen et al., 2005; Koldamova et al., 2005b; Wahrle et al., 2005; Lefterov et al., 2009). Furthermore, ...
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.
Buy anti-Ab1-40 antibody, Rabbit anti-Rat Amyloid Beta Peptide 1-40 (Ab1-40) Polyclonal Antibody (MBS2004399) product datasheet at MyBioSource, Primary Antibodies. Application: Immunocytochemistry (ICC), Immunohistochemistry (IHC) - Formalin/Paraffin, ELISA (EIA), Western Blot (WB)
This will be a multicenter, double-blind (neither investigator nor patient knows which treatment the patient receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), randomized (patients are assigned different treatments based on chance), multiple-dose, proof-of-mechanism (POM) study in pAD. Approximately 24 outpatients (n=8/treatment group) diagnosed with pAD, according to the inclusion and exclusion criteria, will participate in this 4-week treatment study. For all enrolled patients, this study will consist of an 8-week eligibility screening period, a 4-week double-blind treatment period, and a follow-up examination (7-14 days after the last dose). Patients will be assigned randomly to 1 of 3 treatment groups: placebo, JNJ-54861911 10 mg once daily, or JNJ-54861911 50 mg once daily. Safety assessments will be performed throughout the study. The maximal study duration for a patient will be 14 ...
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 ...
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)
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)
In the past, scientists thought amyloid plaques was the problem associated with the disease. Claudio Soto from the University of Texas Medical School of Houston said that it is now clear that those aggregates are not the major culprit but it is the aggregatess precursors. The precursors are a group of molecules called Amyloid-Beta (Aβ) oligomers. Soto continues by saying that it is the main molecule that could be the finest, most reliable means to make an early diagnosis. He also says that is the largest problem in the medical field because physicians cannot identify them until patients are already ill. Soto adds that the amyloid beta oligomers can be in a persons body years or even decades before they show cognitive symptoms.. Soto and his colleagues used a technology they developed to detect misfolded proteins in prion diseases such as Mad Cow Disease. The technology, called protein misfolding cyclic amplification, works by exaggerating existing proteins that misfolded and separating them ...
Alzheimers disease (AD) is characterized by the abnormal aggregation of amyloid-β peptide (Aβ) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in Aβ-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the likelihood of cross-linking, here we designed an Aβ-40 analogue (Aβ-40 Y10F) in which the tyrosine residue was substituted by a structurally similar residue, phenylalanine. The aggregation rate was determined by the Thioflavin T (ThT) assay, in which Aβ-40 Y10F populated an ensemble of folded conformations much quicker and stronger than the wild type Aβ. Biophysical tests subsequently confirmed the results of the ThT assay, suggesting the measured increase of β-aggregation may arise predominantly from enhancement of hydrophobicity upon substitution and thus the propensity of intrinsic β-sheet formation. Nevertheless, Aβ-40 Y10F exhibited remarkably decreased neurotoxicity compared to Aβ-40 which could be
1. Roe CM, Fagan AM, Grant EA, Hassenstab J, Moulder KL, Maue Dreyfus D, Sutphen CL, Benzinger TLS, Mintun MA, Holtzman DM, Morris JC. Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology. 2013;80(19):1784-91. Epub 2013/04/12. doi: 10.1212/WNL.0b013e3182918ca6. PubMed PMID: 23576620; PubMed Central PMCID: PMC3719431. 2. Su Y, DAngelo GM, Vlassenko AG, Zhou G, Snyder AZ, Marcus DS, Blazey TM, Christensen JJ, Vora S, Morris JC, Mintun MA, Benzinger TL. Quantitative analysis of PiB-PET with FreeSurfer ROIs. PLoS One. 2013;8(11):e73377. PubMed PMID: 24223109; PubMed Central PMCID: PMC3819320. 3. Wang L, Brier MR, Snyder AZ, Thomas JB, Fagan AM, Xiong C, Benzinger TL, Holtzman DM, Morris JC, Ances BM. Cerebrospinal Fluid Abeta42, Phosphorylated Tau181, and Resting-State Functional Connectivity. JAMA neurology. 2013. Epub 2013/08/21. doi: 10.1001/jamaneurol.2013.3253. PubMed PMID: 23959173, PMCID: in progress.. 4. Potter R, Patterson BW, Elbert DL, ...
Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimers disease ...
Dennis J. Selkoe, MD, Co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Womens Hospital, discusses progress in the development of Alzheimers disease treatments that target the amyloid beta protein.
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
The protein fragment beta-amyloid tends to accumulate in the brains of people with Alzheimers disease. Early accumulations of beta-amyloid called oligomers may be the most toxic amyloid forms in dementia. A recent study with mice found that oligomers exerted their toxicity through two kinds of receptors, or cellular docking sites. One of these receptors is called the alpha-7 nicotinic acetylcholine receptor (a7nAchR). It is a docking site for cholinergic neurons, which participate in many learning and memory functions. The other receptor type, called the N-methyl-D-aspartate (NMDA) NR2B receptor, is a docking site for glutamate, a chemical messenger in the brain. Study researchers found that stimulation of the nicotinic receptor was associated with oligomer-induced damage to NMDA receptor function. This loss of function, in turn, hindered the ability of neurons to communicate with one another and caused memory problems in the mice.. Min Wang, Ph.D., and colleagues have obtained similar findings ...
Alzheimers disease (AD) is a conformational disease that is characterized by amyloid-β (Aβ) deposition in the brain. Aβ exerts its toxicity in part by receptor-mediated interactions that cause down-stream protein misfolding and aggregation, as well as mitochondrial dysfunction. Recent reports indicate that Aβ may also interact directly with intracellular proteins such as the mitochondrial enzyme ABAD (Aβ binding alcohol dehydrogenase) in executing its toxic effects. Mitochondrial dysfunction occurs early in AD, and Aβs toxicity is in part mediated by inhibition of ABAD as shown previously with an ABAD decoy peptide. Here, we employed AG18051, a novel small ABAD-specific compound inhibitor, to investigate the role of ABAD in Aβ toxicity. Using SH-SY5Y neuroblastoma cells, we found that AG18051 partially blocked the Aβ-ABAD interaction in a pull-down assay while it also prevented the Aβ42-induced down-regulation of ABAD activity, as measured by levels of estradiol, a known hormone and ...
Alzheimer disorder (AD), the most typical source of dementia inside the seniors, is usually seen as a modern cerebral buildup with amyloid-? (A?) stores in a choice dense-core senile plaques or maybe soften amorphous plaques (Just one). Within vivo image scientific tests strongly include the amyloid speculation, which postulates that will structure with senile plaques triggers any pathological cascade leading to recruitment with microglia in addition to induction connected with community neuritic changes nearby the plaques (A pair of, 3 or more). A? is made up generally of 40- plus 42-amino chemical p proteins made on the amyloid forerunner aminoacids (Application) through constant proteolytic cleavages mediated by way of ?- and ?-secretases (Four). Many anti-amyloid treatments are currently inside improvement only several currently have successfully inverted existing amyloid pathology (Two, Five). In regulatable Practical application transgenic rats, any conceptual model for treatments aimed ...
New insights on what causes Alzheimers disease could arise from a recent discovery made by bioengineers from the University of California, San Diego. The finding concerns the infamous amyloid beta peptides (Aβ) -- fragments of which form plaques thought to play a role in Alzheimers disease. The bioengineers found that amyloid beta peptides spontaneously trigger calcium waves in purified cultures of astrocyte cells extracted from the cortex region of rat brains and grown in the lab.
The progressive accumulation of extracellular amyloid plaques in the brain is a common hallmark of Alzheimers disease (AD). We recently
Five point mutations within the amyloid beta-protein (Abeta) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimers disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions. Although a substantial body of data exists on the effects of these mutations on Abeta production, whether or not intra-Abeta mutations alter degradation and how this relates to their aggregation state remain unclear. Here we report that the E22G, E22Q and the D23N substitutions significantly increase fibril nucleation and extension, whereas the E22K substitution exhibits only an increased rate of extension and the A21G substitution actually causes a decrease in the extension rate. These substantial differences in aggregation together with our observation that aggregated wild type Abeta(1-40) was much less well degraded than monomeric wild type Abeta(1-40), prompted us to assess whether or not ...
1IYT: Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion domain.
Introduction: We recently showed that amyloid beta (Aβ) 40 accumulates in erythrocytes and possibly causes cell damage as evidenced from an increased number of
A systematic analysis of Alzheimer disease amyloid β peptide variants inDrosophila brain demonstrates that their predicted propensity to form protofibrillar aggregates correlates best with toxicity.
References for Abcams beta-Amyloid Peptide (35-25) (ab120977). Please let us know if you have used this product in your publication
Natàlia Carullas research group provides information that questions the widely accepted premise regarding the number of molecules and the shape of the first aggregates formed by amyloid beta protein. Amyloid beta protein aggregation, the process by which molecules of this protein adhere to each other is strongly associated with the development of Alzheimers disease. Carullas work ultimately seeks to identify molecules that interfere with the initial stages of aggregation as a strategy to combat the disease.. ...
Clippingdale, Andrew B., Wade, John D. and Barrow, Colin J. 2001, The amyloid-β peptide and its role in Alzheimers disease, Journal of peptide science, vol. 7, no. 5, pp. 227-249, doi: 10.1002/psc.324. ...
Cirrito JR, Disabato BM, Restivo JL, Verges DK, Goebel WD, Sathyan A, Hayreh D, DAngelo G, Benzinger T, Yoon H, Kim J, Morris JC, Mintun MA, Sheline YI (2011). Proc Natl Acad Sci USA, 108(36):14968-73
Peptides , Amyloid Peptides , Beta-Amyloid Peptide Fragments , Beta-Amyloid (1-17)-Cys, Human; This peptide amino acids 1 to 17 is a modified fragment of the b-amyloid peptide, with cysteine substituted for valine at position 17.; DAEFRHDSGYEVHHQKLC; H-Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Cys-OH
Abstract Amyloid-beta peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-beta reduces glutamatergi..
Principal Investigator:AKIYAMA Haruhiko, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Neurology
Cerebral deposition of beta-amyloid peptides (ABeta) is one of the pathological hallmarks of Alzheimers disease. AB is generated by sequential proteolysis of a...
Aggregation can be studied by a range of methods, experimental and computational. Aggregates form in solution, across solid surfaces, and on and in the membrane, where they may assemble into unregulat
1BA4: Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?
Kenneth Collins ,k.p.collins at worldnet.att.net, wrote in news:2NrS8.55528$LC3.4277696 at bgtnsc04-news.ops.worldnet.att.net: , its not a Beta-amyloid thing. the Beta-amyloid thing happens be-cause , normal transcription is prematurely interrupted be-cause latching , neural dynamics are prematurely interrupted. for those who have AoK, , its a TD E/I-minimization ratchet-pawling [Ap5] deficit. , , the point being that, researchers should look-elsewhere, a bit, , starting by looking =carefully= for abnormally-high-frequency , EEG-type traces. the sub-problem, here, is that the global EEG must , be broken into component sub-parts because the correlated , abnormal high-frequency trace[s] will be masked within the global , trace, as the nervous system struggles to compensate with respect to , the failing TD E/I-minimization dynamics. , , shouldnt be difficult to sort it out. , , its definitely =not= a Beta-amyloid thing. I would say that neurodegeneration in Alzheimers mouse ...
Product type: Peptides Product name: Amyloid-Beta 1-40, H14A, Human, Recombinant Description: Recombinant Amyloid-Beta His14Ala peptide 1-40 Format: Lyophilized Molecular
Nucleic Acid Res 2003 - Vol. 31, No.13 (OpenAccess) Science recently featured GlobPlot in NetWatch We did a comparative study of protein disorder and beta aggregation. ...
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
购买Abcam beta-Amyloid多肽(1-11) (CAS 190436-05-6) (ab120834),分子式C56H76N16O22,Amyloidogenic多肽. beta-Amyloid多肽(1-11).。
Duka V.; Bestel I.; Segalen V.; Czaplewski C.; Liwo A.; Liepina I. Amiloīda beta proteīna 25-35 beta-sloksnes un beta-sloksņu grēdas molekulārā modelēšana = Molecular Modeling of Single Beta-Sheet and the Beta-Sheet Stack of Amyloid Beta Protein 25-35 = Молекулярное моделирование одного бета-листа и стека из бета-листов белка бета-амилоид 25-35. RTU zin.raksti. Sēr.1. 2011, Sēj.23. Materiālzinātne un lietišķā ķīmija = Material Science and Applied Chemistry, 62-72 ...
JPT Peptide Technologies is a DIN ISO 9001:2015 certified and GCLP compliant integrated provider of innovative peptide based catalog products and custom services.
Sigma-Aldrich offers abstracts and full-text articles by [Stefania Mondello, Andras Buki, Pal Barzo, Jeff Randall, Gail Provuncher, David Hanlon, David Wilson, Firas Kobeissy, Andreas Jeromin].
The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimers disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta. ...
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 ...
... , vigilin interacts with signal peptide peptidase inhibitor, naturietic peptide, lipopeptide peptide bond, human c peptide rian, natural ways to treat depression and anxiety, natriuretic peptide receptor inhibitors, minecraft aura glp 2 peptide, peptide tx2 6, how is peptide bond broken through hydrolysis, web expasy org peptide mass ca, nexigen peptide, peptide mass spectra of organic compounds, peptide based face care product, bromoethylamine cysteine peptide, eps 2014 peptide calculator, beta peptide circular dichroism secondary, peptide drug delivery colonic and rectal absorption, tri peptide cell activator reviews
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 ...
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 ...
Abstract: In Alzheimers disease, the neuritic or senile amyloid plaques in hippocampus and association cortex, the diffuse plaques in brain areas such as the cerebellum and sensorimotor cortex, and the amyloid deposits in the walls of pial and parenchymal blood vessels are mainly composed of amyloid β-peptides. In the present study, either soluble 40-residue amyloid β-peptide radiolabeled with 125I (I-sAβ) or [14C]polyethylene glycol ([14C]-PEG, a reference material) was briefly infused into one lateral ventricle of normal rats. By 3.5 min, 30% of the I-sAβ was cleared from ventricular CSF into blood; another 30% was removed over the next 6.5 min. No [14C]PEG was lost from the CSF-brain system during the first 5 min, and only 20% was cleared by 10 min. Much of the I-sAβ that reached the subarachnoid space was retained by pial arteries and arterioles. Virtually no I-sAβ was found in brain. The clearance of amyloid β-peptides from the CSF-brain system, reported herein for normal rats, may ...
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 ...
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 genetically linked to the processing of amyloid b protein precursor (AbPP). Aside from being the precursor of the Amyloid
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. ...
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. ...
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 ...
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., ...
Four human B cell lines established by Epstein-Barr viral transformation of B cells from a patient with a clinical diagnosis of Alzheimers disease (AD) were found to secrete antibodies that react with plaques and cerebrovascular blood vessels in AD brain in a staining profile characteristic of beta-amyloid protein (beta-AP) in AD brain. Two of these antibodies were shown to be reactive with a rare plaque in a normal brain. In these studies, immunofluorescence and avidin-biotin complex immunoperoxidase methodology were used to determine antibody reaction, and thioflavine S was used to double label amyloid and neurofibrillary tangles. The four antibodies also reacted with neurons in normal and AD brain. Absorption studies, dot immunoblots, and enzyme-linked immunosorbent assays with beta-amyloid peptides 1-28 (beta-A1-28) and 1-40 (beta-A1-40) indicate the major determinant of the reactive epitope is located in the region of amino acids 1-28 of beta-AP. However, inhibition studies demonstrate a ...
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: http://eprints.uwe.ac.uk/1512 Full text not available from this repository. Publishers URL: http://dx.doi.org/10.1016/j.neurobiolaging.2004.07... ...
This laboratory has as a major focus the study of neuropeptidases and their involvement in human disease. It is generally believed that Alzheimers disease is caused by the accumulation of a peptide called the amyloid beta peptide in the brain of affected individuals. Two peptidases, neprilysin and insulysin, are involved in regulating amyloid beta peptide levels in the brain. It is believed that a there is an age dependent decline in the activity of these enzymes which leads to increased amyloid beta peptide levels as a contributing factor to Alzheimers disease. We are investigating strategies based on gene replacement therapies to use these peptidases to lower brain amyloid beta peptide levels as a method to prevent and treat Alzheimers disease. We are also styudying the role of these peptidases in diabetes as they can cleave amylin, a related peptide that has been implicated in causing type 2 diabetes.. ...
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; ...
The etiology of Alzheimers disease (AD) is complex with oxidative stress being a possible contributory factor to pathogenesis and disease progression. TASTPM transgenic mice expressing familial AD-associated amyloid precursor protein (APPswe) and presenilin transgenes (PS1M146V) show increased brain amyloid beta (Abeta) levels and Abeta plaques from 3 months. We tested if enhancing oxidative stress through diet would accelerate Abeta-related pathology. TASTPM were fed a pro-oxidant diet for 3 months resulting in increased brain levels of protein carbonyls, increased Nrf2, and elevated concentrations of glutathione (GSH). The diet increased both amyloid precursor protein (APP) and Abeta in the cortex of TASTPM but did not alter Abeta plaque load, presenilin 1, or beta-secretase (BACE1) expression. TASTPM cortical neurons were cultured under similar pro-oxidant conditions resulting in increased levels of APP and Abeta likely as a result of enhanced beta/gamma secretase processing of APP. Thus, ...
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.
Alzheimers disease is the worlds most common dementing illness. Deposition of amyloid-β peptide drives cerebral neuroinflammation by activating microglia. Indeed, amyloid-β activation of the NLRP3 inflammasome in microglia is fundamental for interleukin-1β maturation and subsequent inflammatory events. However, it remains unknown whether NLRP3 activation contributes to Alzheimers disease in vivo. Here we demonstrate strongly enhanced active caspase-1 expression in human mild cognitive impairment and brains with Alzheimers disease, suggesting a role for the inflammasome in this neurodegenerative disease. Nlrp3(-/-) or Casp1(-/-) mice carrying mutations associated with familial Alzheimers disease were largely protected from loss of spatial memory and other sequelae associated with Alzheimers disease, and demonstrated reduced brain caspase-1 and interleukin-1β activation as well as enhanced amyloid-β clearance. Furthermore, NLRP3 inflammasome deficiency skewed microglial cells to an M2 ...
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, ...
There is compelling evidence supporting amyloid as one of the key pathologic agents in AD. Autopsy studies suggest the amount and location of fibrillar amyloid deposition does not relate strongly to the degree and type of clinical impairment, compared to tau pathology and neuronal loss. A substantial percentage of individuals known to be cognitively intact prior to death demonstrate significant amyloid pathology at autopsy. PIB-PET studies of older normal individuals have also demonstrated significant amyloid deposition in substantial percentages.. This study will test the hypothesis that amyloid is associated with synaptic dysfunction and neuronal damage. While some individuals are able to compensate for amyloid-related toxicity for an extended time period, sensitive imaging and neuropsychological markers will reveal that normal subjects with evidence of high amyloid burden do demonstrate evidence of abnormality consistent with prodromal AD.. The study will use a combination of functional, ...
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 ...
Amyloid beta-protein (A beta) is a proteolytic fragment of the amyloid beta-protein precursor (beta PP). Progressive cerebral deposition of A beta is an early and invariant feature of Alzheimers disease. The cellular trafficking of beta PP is of particular interest because understanding the production of A beta requires a comprehensive elucidation of the metabolic pathways of this protein. In addition, beta PP is a type I integral membrane glycoprotein that belongs to a class of molecules with both full length and secreted products. Recent evidence suggests that beta PP can be processed in an endosomal/lysosomal pathway. In the latter organelles, a number of beta PP carboxy-terminal derivatives are found, but the precise pathway and kinetics of beta PP trafficking from the cell surface remain unclear. To address these questions, we visualized directly the beta PP internalization pathway by following the localization and distribution of beta PP monoclonal antibodies added to intact beta ...
Beta amyloid (Aβ) deposits are seen in aged individuals in many of the mammalian species that possess the same Aβ amino acid sequence as humans. Conversely, neurofibrillary tangles (NFT), the other hallmark lesion of Alzheimers disease (AD), are extremely rare in these animals. We detected Aβ deposits in the brains of Tsushima leopard cats (Prionailurus bengalensis euptilurus) that live exclusively on Tsushima Island, Japan. Aβ42 was deposited in a granular pattern in the neuropil of the pyramidal cell layer, but did not form argyrophilic senile plaques. These Aβ deposits were not immunolabeled with antibodies to the N-terminal of human Aβ. Sequence analysis of the amyloid precursor protein revealed an amino acid substitution at the 7th residue of the Aβ peptide. In a comparison with other mammalian animals that do develop argyrophilic senile plaques, we concluded that the alternative Aβ amino acid sequence displayed by leopard cats is likely to be related to its distinctive deposition pattern.
Small heat shock protein HspB8: its distribution in Alzheimers disease brains s inhibition of amyloid-beta protein aggregation and cerebrovascular d-beta toxicity ...
Ly et al: CAA Predisposes to rt-PA Related Hhemorrhage Cerebral b-Amyloid Detected by Pittsburgh Compound B Positron Emission Topography Predisposes to Recombinant Tissue Plasminogen Activator-Related Hemorrhage John V. Ly,1 Christopher C. Rowe,2 Victor L. Villemagne,2 Jorge A. Zavala,1 Henry Ma,1 Graeme OKeefe,2 Sylvia J. Gong,2 Rico Gunawan,1 Leonid Churilov,1 Tim Saunder,2 Uwe Ackerman,2 Henri Tochon-Danguy,2 and Geoffrey A. Donnan1,3 Cerebral amyloid angiopathy (CAA) may be an important predisposing factor for the hemorrhagic complications of recombinant tissue-type plasminogen activator (rt-PA) therapy. We studied patients treated within 3 hours of onset of ischemic stroke with rt-PA using positron emission tomography to compare Pittsburgh compound B (PiB) (a cerebral b-amyloid ligand) retention in those with and without parenchymal hemorrhage (PH) and normal controls. Neocortical PiB retention was higher among patients with PH compared with patients without PH and normal controls, ...
Neuritic plaques and neurofibrillary tangles are crucial morphological criteria for the definite diagnosis of Alzheimers disease. We evaluated 12 unstained frontal cortex and hippocampus samples from 3 brain donors with Alzheimers disease and 1 control with hyperspectral Raman microscopy on samples of 30 × 30 µm. Data matrices of 64 × 64 pixels were used to quantify different tissue components including proteins, lipids, water and beta-sheets for imaging at 0.47 µm spatial resolution. Hierarchical cluster analysis was performed to visualize regions with high Raman spectral similarities. The Raman images of proteins, lipids, water and beta-sheets matched with classical brain morphology. Protein content was 2.0 times, the beta-sheet content 5.6 times and Raman broad-band autofluorescence was 2.4 times higher inside the plaques and tangles than in the surrounding tissue. The lipid content was practically equal inside and outside. Broad-band autofluorescence showed some correlation with ...
que es el Alzheimer? Alzheimers Disease Research Center at University of California, Los Angles (UCLA) also enrolls patients and subjects in clinical and pre-clinical research program. Alzheimers Disease NeuroImaging Initiative (ADNI) is a brain imaging and biomarkers, and longitudinal studies. We have bilingual staff that speaks Spanish and English. UCLA Alzheimers Disease Research Center is located in Los Angeles, California.
High fat/high cholesterol diets exacerbate β-amyloidosis in mouse models of Alzheimers disease (AD). It has been impossible, however, to study the relationship between atherosclerosis and β-amyloidosis; in those models because such mice were on atherosclerosis-resistant genetic backgrounds. Here we report the establishment of AD model mice, B6Tg2576, that are prone to atherosclerosis. B6Tg2576 mice were produced by back-crossing Tg2576 mice, an AD mouse model overexpressing human amyloid β-protein precursor with the Swedish double mutation, to C57BL/6 mice, a strain susceptible to diet-induced atherosclerosis. An atherogenic diet induced aortic atherosclerosis and exacerbated cerebral β-amyloidosis in B6Tg2576 mice. Compared with age-matched non-transgenic littermates, B6Tg2576 mice developed significantly more diet-induced aortic atherosclerosis. Unexpectedly, normal diet-fed B6Tg2576 mice also developed fatty streak lesions (early atherosclerosis) in the aorta. The aortic atherosclerotic ...
Alzheimers disease, Familial British dementia, Familial Danish dementia, Type 2 diabetes mellitus, plus Creutzfeldt-Jakob disease are associated with amyloid fibril deposition and oxidative stress. The antioxidant enzyme catalase is a neuroprotective amyloid binding protein. Herein the effects of catalase overexpression in SH-SY5Y neuronal cells on the toxicity of amyloid-β (Aβ), amyloid-Bri (ABri), amyloid-Dan (ADan), amylin (IAPP), and prion protein (PrP) peptides were determined. Results showed catalase overexpression was neuroprotective against Aβ, ABri, ADan, IAPP, and PrP peptides. The catalase inhibitor 3-amino-1,2,4-triazole (3-AT) and catalase-amyloid interaction inhibitor benzothiazole aniline tetra(ethylene glycol) (BTA-EG4) significantly enhanced neurotoxicity of amyloid peptides in catalase overexpressing neuronal cells. This suggests catalase neuroprotection involves breakdown of hydrogen peroxide (H2O2) plus a direct binding interaction between catalase and the Aβ, ABri, ...

Intracellular biology of Alzheimers disease amyloid beta peptide | SpringerLinkIntracellular biology of Alzheimer's disease amyloid beta peptide | SpringerLink

Originally this peptide, beta-amyloid 42 (Aβ42), was assumed to be released by a... ... Strong evidence links excess production of a small peptide and the pathogenesis of Alzheimers disease (AD). ... Originally this peptide, beta-amyloid 42 (Aβ42), was assumed to be released by a pathogenic event; it is now well established ... Key words Cell biology Endoplasmic reticulum Golgi trans Golgi network Amyloid Alzheimers ¶disease ...
more infohttps://link.springer.com/article/10.1007%2Fs004060050102

amyloid beta peptides Protocols and Video...'amyloid beta peptides' Protocols and Video...

A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and Amyloid Beta 40 Peptides, Capable of Oligomer ... amyloid beta peptides include Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/ ... Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus, Standards for Quantitative Metalloproteomic ... A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis, In Vitro Assays to Assess Blood-brain ...
more infohttps://www.jove.com/keyword/amyloid+beta+peptides

Alpha-helix targeting reduces amyloid-beta peptide toxicity.Alpha-helix targeting reduces amyloid-beta peptide toxicity.

... Nerelius C., Sandegren A., Sargsyan H., Raunak R., Leijonmarck H. ... The amyloid-beta peptide (Abeta) can generate cytotoxic oligomers, and their accumulation is thought to underlie the ...
more infohttps://www.uniprot.org/citations/19458258

Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide ProductionCalcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide Production

... Mark A. Lovell,1,2 Erin ... and Effects on Amyloid Beta Peptide Production," Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 787805, 9 ...
more infohttps://www.hindawi.com/journals/omcl/2015/787805/cta/

Serum Amyloid Beta Peptides in Patients with Dementia and Age-Mat...: Ingenta ConnectSerum Amyloid Beta Peptides in Patients with Dementia and Age-Mat...: Ingenta Connect

Serum Amyloid Beta Peptides in Patients with Dementia and Age-Matched Non-Demented Controls as Detected by Surface-Enhanced ... Keywords: Alzheimers Disease; CSF profile; DNA Isolation; Genotype Analysis; SELDI-TOF MS; Serum Amyloid Beta Peptides; ... Results: Aß37, Aß38 and Aß40 were found among additional unidentified Aß peptides, with the most pronounced Aß peak at a ... Background: By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDITOF MS) an amyloid ß ...
more infohttp://www.ingentaconnect.com/content/ben/ccp/2008/00000003/00000003/art00001

Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimers DiseaseZinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease

Alzheimers disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A. 𝛽. -)peptides ... Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimers Disease. Mallory ... peptides. In addition, other members of the zinc metalloproteinase family can degrade preformed A. 𝛽. -peptides. As such, the ... peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to ...
more infohttps://www.hindawi.com/journals/bri/2011/721463/abs/

How can local environmental conditions influence the secondary structure of an amyloid beta peptide?How can local environmental conditions influence the secondary structure of an amyloid beta peptide?

... ... How can local environmental conditions influence the secondary structure of an amyloid beta peptide? ... How can local environmental conditions influence the secondary structure of an amyloid beta peptide? ... The neurotoxicity of their main components, the amyloid b peptides (Aβs), may be mediated by their direct interaction with the ...
more infohttp://www.esrf.eu/home/UsersAndScience/Publications/Highlights/highlights-2014/XRI/XRI11.html

RCSB PDB 









- 1IYT: Solution structure of the Alzheimers disease amyloid beta-peptide (1-42) Literature Report PageRCSB PDB - 1IYT: Solution structure of the Alzheimer's disease amyloid beta-peptide (1-42) Literature Report Page

Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion ... Alzheimers disease amyloid A 42 Homo sapiens Fragment: beta-peptide Gene Name(s): APP Gene View A4 AD1 ... Solution structure of the Alzheimers disease amyloid beta-peptide (1-42). *DOI: 10.2210/pdb1iyt/pdb ...
more infohttp://www.rcsb.org/pdb/explore/litView.do?structureId=1IYT

Sequence Similarity 









- 1IYT: Solution structure of the Alzheimers disease amyloid beta-peptide (1-42) Sequence...Sequence Similarity - 1IYT: Solution structure of the Alzheimer's disease amyloid beta-peptide (1-42) Sequence...

Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion ... Alzheimers disease amyloid protein, length: 42 (BLAST) Sequence Similarity Cutoff. Rank. Chains in Cluster. Cluster ID / Name ...
more infohttp://www.rcsb.org/pdb/explore/sequenceCluster.do?structureId=1IYT

Amyloid-beta peptide behind Alzheimer - for the first time hydrogen bonds were analysed - Healthcanal.com : Healthcanal.comAmyloid-beta peptide behind Alzheimer - for the first time hydrogen bonds were analysed - Healthcanal.com : Healthcanal.com

Amyloid-beta peptide that causes nerve cell death in Alzheimers patients brain. When Amyloid-beta, forms small aggregates, ... Thanks to these new results, there is a successful method avaliable - for analysis of structure of Amyloid-beta peptides in ... However, the molecular structure of these tiny oligomers of Amyloid-beta peptide, is yet unknown today. Therefore, it is ... Amyloid-beta peptide behind Alzheimer - for the first time hydrogen bonds were analysed. ...
more infohttps://www.healthcanal.com/brain-nerves/33606-amyloid-beta-peptide-behind-alzheimer-for-the-first-time-hydrogen-bonds-were-analysed.html

Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset...Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset...

To follow up on this suggestion, we compared the binding of synthetic amyloid beta (beta/A4) peptide to purified apoE4 and ... Binding of beta/A4 peptide by oxidized apoE may determine the sequestration or targeting of either apoE or beta/A4 peptide, and ... In addition, apoE4 did not bind beta/A4 peptide at pH , 6.6, whereas apoE3 bound beta/A4 peptide from pH 7.6 to 4.6. Together ... Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset ...
more infohttps://www.pnas.org/content/90/17/8098?ijkey=403a4e26606295740494851c22513d58412e733a&keytype2=tf_ipsecsha

Acetylcholinesterase-amyloid-beta-peptide interaction: effect of Congo Red and the role of the Wnt pathway. | Sigma-AldrichAcetylcholinesterase-amyloid-beta-peptide interaction: effect of Congo Red and the role of the Wnt pathway. | Sigma-Aldrich

Acetylcholinesterase-amyloid-beta-peptide interaction: effect of Congo Red and the role of the Wnt pathway.. [Nibaldo C ... Such inhibitors prevent the aggregation of amyloid-beta-peptide (Abeta) into Alzheimers fibrils. The incorporation of AChE, as ... Finally, recent studies are consistent with the idea that a attenuating beta-catenin loss of function of Wnt signaling ... which is one of the several proteins associated with amyloid plaque deposits. Recently, novel dual inhibitors of AChE have been ...
more infohttps://www.sigmaaldrich.com/catalog/papers/15974895

Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimers...Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's...

Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimers ... the presence of oligomers of amyloid beta-peptide (Abeta), and synapse loss. In this review we discuss the role of Abeta in the ... Roles of Amyloid β-Peptide-Associated Oxidative Stress and Brain Protein Modifications in the Pathogenesis of Alzheimers ... Roles of Amyloid β-Peptide-Associated Oxidative Stress and Brain Protein Modifications in the Pathogenesis of Alzheimers ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/17664130

Analysis of Neurotoxic Beta Amyloid Peptides in Alzheimers DiseaseAnalysis of Neurotoxic Beta Amyloid Peptides in Alzheimer's Disease

This article briefly explains the production of Aß from amyloid precursor protein (APP). ... Alzheimers disease is characterized by the presence of neurotoxic beta amyloid (Aß) deposits in the brain. ... Analysis of Neurotoxic Beta Amyloid Peptides in Alzheimers Disease. *Download PDF Copy ... 2019, April 01). Analysis of Neurotoxic Beta Amyloid Peptides in Alzheimers Disease. News-Medical. Retrieved on December 12, ...
more infohttps://www.news-medical.net/whitepaper/20171215/Analysis-of-Neurotoxic-Beta-Amyloid-Peptides-in-Alzheimers-Disease.aspx

beta-Amyloid Peptide (35-25) References | Abcambeta-Amyloid Peptide (35-25) References | Abcam

References for Abcams beta-Amyloid Peptide (35-25) (ab120977). Please let us know if you have used this product in your ... Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By ...
more infohttp://www.abcam.com/beta-amyloid-peptide-35-25-ab120977-references.html

Towards physico-chemical understanding of fibril formation of the Alzheimer disease-associated amyloid beta-peptideTowards physico-chemical understanding of fibril formation of the Alzheimer disease-associated amyloid beta-peptide

... Linse, ... Towards physico-chemical understanding of fibril formation of the Alzheimer disease-associated amyloid beta-peptide}, volume ...
more infohttps://lup.lub.lu.se/search/publication/1461639

Protective Effects of Walnut Extract Against Amyloid Beta Peptide-Induced Cell Death and Oxidative Stress in PC12 Cells |...Protective Effects of Walnut Extract Against Amyloid Beta Peptide-Induced Cell Death and Oxidative Stress in PC12 Cells |...

... is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimers disease. Aβ is ... LeVine H III (1993) Thioflavine T interaction with synthetic Alzheimers disease beta-amyloid peptides: detection of amyloid ... The relationship between the aggregational state of the amyloid-beta peptides and free radical generation by the peptides. J ... Sponne I, Fifre A, Drouet B et al (2003) Apoptotic neuronal cell death induced by the non-fibrillar amyloid-beta peptide ...
more infohttps://link.springer.com/article/10.1007%2Fs11064-011-0533-z

Photo-biomodulation and soybean isoflavones on amyloid-beta peptide-induced oxidative stress and inflammationPhoto-biomodulation and soybean isoflavones on amyloid-beta peptide-induced oxidative stress and inflammation

... and the aggregation of amyloid-[beta]-peptide (A[beta]) is recognized as one of the prevailing pathology of AD. There is a ... Photo-biomodulation and soybean isoflavones on amyloid-beta peptide-induced oxidative stress and inflammation. Tao, Biwen ... beta] (IL-1[beta]) and inducible nitric-oxide synthase (iNOS). In this study, two different treatment strategies have been ... In the present study, both laser light treatment and soybean isoflavones treatment showed the ability to suppress A[beta]- ...
more infohttps://mospace.umsystem.edu/xmlui/handle/10355/40225

beta-Amyloid Peptide (1-40) (human) References | Abcambeta-Amyloid Peptide (1-40) (human) References | Abcam

References for Abcams beta-Amyloid Peptide (1-40) (human) (ab120479). Please let us know if you have used this product in your ... Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By ...
more infohttp://www.abcam.com/beta-amyloid-peptide-1-40-human-ab120479-references.html

Dynamic micellar oligomers of amyloid beta peptides play a crucial role in their aggregation mechanisms - Physical Chemistry...Dynamic micellar oligomers of amyloid beta peptides play a crucial role in their aggregation mechanisms - Physical Chemistry...

A deep understanding of the early molecular mechanism of amyloid beta peptides (Aβ) is crucial to develop therapeutic and ... Dynamic micellar oligomers of amyloid beta peptides play a crucial role in their aggregation mechanisms B. Morel, M. P. ... Dynamic micellar oligomers of amyloid beta peptides play a crucial role in their aggregation mechanisms† ... A deep understanding of the early molecular mechanism of amyloid beta peptides (Aβ) is crucial to develop therapeutic and ...
more infohttps://pubs.rsc.org/en/content/articlelanding/2018/CP/C8CP02685H

PRIME PubMed | Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimers disease brain...PRIME PubMed | Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain...

PubMed journal article Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimers disease ... central role for amyloid beta-peptide.. *Aging, gender and APOE isotype modulate metabolism of Alzheimers Abeta peptides and F ... Amyloid beta-Peptides. Cell Death. Humans. Lipid Peroxidation. Neurons. Pub Type(s). Journal Article. Research Support, U.S. ... Amyloid beta-peptide [Abeta(1-42)] is central to the pathogenesis of Alzheimers disease (AD), and the AD brain is under ...
more infohttps://www.unboundmedicine.com/medline/citation/12392766/Evidence_that_amyloid_beta_peptide_induced_lipid_peroxidation_and_its_sequelae_in_Alzheimer

DK2379601T3 - Anti-idiotypic antibody to an antibody to amyloid BETA PEPTIDE 
        - Google PatentsDK2379601T3 - Anti-idiotypic antibody to an antibody to amyloid BETA PEPTIDE - Google Patents

Humanized antibodies that recognize beta amyloid peptide EP1432444A4 (en) * 2001-08-17. 2005-11-02. Lilly Co Eli. Anti-a-beta ... Human anti-amyloid .beta. peptide antibody and fragment of said antibody KR101068289B1 (en) * 2004-07-30. 2011-09-28. 리나트 ... uncheck the amyloid-beta peptide humanized antibodies, PE05742002A1 (en) * 2000-12-06. 2002-07-02. Wyeth Corp. Humanized ... Antibodies directed against amyloid-beta peptide and methods using same AR051528A1 (en) * 2004-12-15. 2007-01-17. Neuralab Ltd ...
more infohttps://patents.google.com/patent/DK2379601T3/en

Beta-Amyloid Peptide (1-42), mouse, ratBeta-Amyloid Peptide (1-42), mouse, rat

Amyloid Peptides , Beta-Amyloid Peptides - Mouse,Rat , Beta-Amyloid Peptide (1-42), mouse, rat; ... Peptides , Amyloid Peptides , Beta-Amyloid Peptides - Mouse/Rat ,, Beta-Amyloid Peptide (1-42), mouse, rat. ... 2003). Adult mouse astrocytes degrade amyloid-bold beta in vitro and in situ. Nature Med 9, 453. doi: 10.1038/nm838. Sawamura, ...
more infohttps://anaspec.com/products/product.asp?id=30322

Human beta-Amyloid Peptide 1-42Human beta-Amyloid Peptide 1-42

... peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by ß-secretases and ... Amyloid Beta (Aβ) peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by ... alzheimer disease amyloid protein, cerebral vascular amyloid peptide, APP, Amyloid Precursor Protein Ave. Rating Submit a ... binding to plate-immobilized Human β-Amyloid Peptide (1-42). ELISA was performed by coating wells with 10 ng of Human β-Amyloid ...
more infohttps://www.biolegend.com/it-it/products/human-beta-amyloid-peptide-1-42-15702

Human beta-Amyloid Peptide 1-40Human beta-Amyloid Peptide 1-40

... beta-amyloid peptide, alzheimer disease amyloid protein, cerebral vascular amyloid peptide, APP, Amyloid Precursor Protein Ave ... Amyloid Beta (Aβ) peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by ... binding to plate-immobilized Human β-Amyloid Peptide (1-40). ELISA was performed by coating wells with 10 ng of Human β-Amyloid ... binding to plate-immobilized Human β-Amyloid Peptide (1-40). ELISA was performed by coating wells with 10 ng of Human β-Amyloid ...
more infohttps://www.biolegend.com/fr-lu/products/human-beta-amyloid-peptide-1-40-15882
  • Binding of beta/A4 peptide by oxidized apoE may determine the sequestration or targeting of either apoE or beta/A4 peptide, and isoform-specific differences in apoE binding or oxidation may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease. (pnas.org)
  • We used the 6E10 antibody and immunopurified Aβ peptides and glycopeptides from CSF samples and then liquid chromatography-tandem mass spectrometry for structural analysis using collision-induced dissociation and electron capture dissociation. (uniprot.org)
  • Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. (wikipedia.org)
  • Bimolecular nucleation appears to occur at low peptide concentration while above the critical micellar concentration, the nucleation takes place more efficiently in the micelles. (rsc.org)
  • To follow up on this suggestion, we compared the binding of synthetic amyloid beta (beta/A4) peptide to purified apoE4 and apoE3, the most common isoform. (pnas.org)
  • A recombinant human matriptase protease domain was used to cleave a synthetic human Aβ1-42 peptide. (springer.com)
  • No. 3946-SEB-010) and a synthetic human Aβ1-42 peptide (Cat. (springer.com)
  • The human Aβ1-42 peptide can be cleaved by the matriptase serine protease domain, at Arg-5, Lys-16, and Lys-28, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. (springer.com)
  • Inhibitors have been designed with the aim of developing analgesic and antihypertensive agents that act by preventing neprilysin's activity against signaling peptides such as enkephalins, substance P, endothelin, and atrial natriuretic factor. (wikipedia.org)
  • We observed an increase of up to 2.5 times of Tyr10 glycosylated Aβ peptides in CSF in six AD patients compared to seven non-AD patients. (uniprot.org)
  • Complementary information on the crystalline fractions of the lipid and peptide system was obtained by micro small and wide angle X-ray scattering (μSAXS/WAXS). (esrf.eu)
  • Further work could help to clarify the role of enzymes, such as acetylcholinesterase, and of different lipid systems in the amyloidosis of the analysed peptides and of other Aβ fragments. (esrf.eu)
  • Objective: To investigate the Aβ-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of Aβ-peptide-peaks in serum and clinical, demographical and genetic variables. (ingentaconnect.com)
  • APP cleavages by α- and γ-secretases release the non-toxic P3 peptide, precluding the production of Aβ1-40 or Aβ1-42. (springer.com)
  • Together these results indicate differences in the two isoforms in complexing with the beta/A4 peptide. (pnas.org)
  • Results: Aß37, Aß38 and Aß40 were found among additional unidentified Aß peptides, with the most pronounced Aß peak at a molecular mass of 7752. (ingentaconnect.com)