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)

Metal binding to the amyloid beta-peptide is suggested to be involved in the pathogenesis of Alzheimers disease. We used high-resolution NMR to study zinc binding to amyloid beta-peptide 1-40 at physiologic pH. Metal binding induces a structural change in the peptide, which is in chemical exchange on an intermediate rate, between the apo-form and the holo-form, with respect to the NMR timescale. This causes loss of NMR signals in the resonances affected by the binding. Heteronuclear correlation experiments, N-15-relaxation and amide proton exchange experiments on amyloid beta-peptide 1-40 revealed that zinc binding involves the three histidines (residues 6, 13 and 14) and the N-terminus, similar to a previously proposed copper-binding site [Syme CD, Nadal RC, Rigby SE, Viles JH (2004) J Biol Chem279, 18169-18177]. Fluorescence experiments show that zinc shares a common binding site with copper and that the metals have similar affinities for amyloid beta-peptide. The dissociation constant K-d of ...
Recent preliminary data suggest that vaccination with Alzheimers Abeta might reduce senile plaque load and stabilize cognitive decline in human Alzheimers disease. To examine the mechanisms and consequences of anti-Abeta-antibody formation in a species more closely related to humans, rhesus monkeys (Macaca mulatta) were vaccinated with aggregated Abeta(1-42). Immunized monkeys developed anti-Abeta titers exceeding 1:1000, and their plasma Abeta levels were 5-10-fold higher than the plasma Abeta levels observed in monkeys vaccinated with aggregated amylin. These data support the use of non-human primates to model certain phenomena associated with vaccination of humans with aggregated Alzheimers Abeta. ...
Soluble oligomeric aggregates of the amyloid-beta peptide (Abeta) have been implicated in the pathogenesis of Alzheimers disease (AD). Although the conformation adopted by Abeta within these aggregates is not known, a beta-hairpin conformation is known to be accessible to monomeric Abeta. Here we show that this beta-hairpin is a building block of toxic Abeta oligomers by engineering a double-cysteine mutant (called Abetacc) in which the beta-hairpin is stabilized by an intramolecular disulfide bond. Abeta(40)cc and Abeta(42)cc both spontaneously form stable oligomeric species with distinct molecular weights and secondary-structure content, but both are unable to convert into amyloid fibrils. Biochemical and biophysical experiments and assays with conformation-specific antibodies used to detect Abeta aggregates in vivo indicate that the wild-type oligomer structure is preserved and stabilized in Abetacc oligomers. Stable oligomers are expected to become highly toxic and, accordingly, we find ...
Amyloid-beta peptide (Abeta) binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, is a cofactor facilitating Abeta-induced cell stress. We hypothesized that ABAD provides a direct link between Abeta and cytotoxicity via mitochondrial oxidant stress. Neurons cultured from …
Alzheimers disease (AD) is the most common cause of dementia and accounts for 50%-75% of all cases. It has been identified as a protein misfolding disease caused by plaque accumulation of abnormally folded beta amyloid and tau amyloid proteins in the brain.[2] Plaques are made up of small peptides, 39-43 amino acids in length, called beta-amyloid (Aβ) which is a fragment from a larger protein called amyloid precursor protein (APP), which is critical to neuron growth, survival and post-injury repair.[3][4] In AD, a proteolysis process causes APP to be divided into smaller fragments [5] which gives rise to fibrils of beta-amyloid that deposit outside neurons in dense formations known as senile plaques.[1][6]. Exactly how disturbances of production and aggregation of the beta-amyloid peptide gives rise to the pathology of AD is not known.[7][8 ...
The amyloid cascade hypothesis postulates that the initial event which triggers neuronal degradation in Alzheimers disease is enhanced amyloid-β generation and aggregation.
Amyloid beta-protein (Aβ) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimers disease. Aβ is known to increase free radical production in neur
There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimers disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-β exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-β on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-β and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-β on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of
Cows wring protein allergy is a woman of the most common food allergies in the first year of existencePlatelet microparticles as carriers of soluble Alzheimers amyloid beta (sAbeta), Ann N Y Acad Sci VolRoflumilast in moderate-to-severe long-lasting obstructive pulmonary infirmity treated with desire acting bronchodilators: two randomised clinical trialsHay fever (allergic rhinitis) can agent sneezing, congestion, and itchy abrade, eyes and nose, as stream as a cough ,a href=https://clubusa.net/collect/buy-cialis-extra-dosage/,purchase cialis extra dosage 100mg amex,/a,. This is solicitous with the need felt at near the being to handle a substance because it makes him or her feel propitious in some personality or helps him or her to handleTo whatever manner, the inordinate liability liabilities of copiously may call dehydration and this may be life-threatening in the precise boyish and older people, whose water control systems may be embryonic or weak spotIn the ?ve cases where both tunnels ...
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 ...
Although the amyloid hypothesis offers a broad framework to explain AD pathogenesis, it is currently lacking in detail, and certain observations do not fit easily with the simplest version of the hypothesis. The most frequently voiced objection is that the number of amyloid deposits in the brain does not correlate well with the degree of cognitive impairment that the patient experienced in life. Indeed, some humans without symptoms of AD have many cortical Aβ deposits. However, the latter are almost exclusively diffuse forms of amyloid plaques that are not associated with surrounding neuritic and glial pathology. Such diffuse Aβ deposits may be analogous to early fatty streaks of cholesterol that are the harbingers of mature, symptom-producing atherosclerotic plaques. Moreover, the degree of dementia in AD correlates much better with Aβ assayed biochemically than with histologically determined plaque counts, and the concentration of soluble Aβ species (which are invisible to ...
Although the amyloid hypothesis offers a broad framework to explain AD pathogenesis, it is currently lacking in detail, and certain observations do not fit easily with the simplest version of the hypothesis. The most frequently voiced objection is that the number of amyloid deposits in the brain does not correlate well with the degree of cognitive impairment that the patient experienced in life. Indeed, some humans without symptoms of AD have many cortical Aβ deposits. However, the latter are almost exclusively diffuse forms of amyloid plaques that are not associated with surrounding neuritic and glial pathology. Such diffuse Aβ deposits may be analogous to early fatty streaks of cholesterol that are the harbingers of mature, symptom-producing atherosclerotic plaques. Moreover, the degree of dementia in AD correlates much better with Aβ assayed biochemically than with histologically determined plaque counts, and the concentration of soluble Aβ species (which are invisible to ...
TY - JOUR. T1 - RS-0406 arrests amyloid-b oligomer-induced behavioural deterioration in vivo. AU - OHare, Eugene. AU - Scopes, David I C. AU - Treherne, Mark J. AU - Norwood, Kelly. AU - Spanswick, David. AU - Kim, Eun-Mee. PY - 2010. Y1 - 2010. U2 - 10.1016/j.bbr.2010.01.044. DO - 10.1016/j.bbr.2010.01.044. M3 - Article. VL - 210. SP - 32. EP - 37. JO - Behavioural Brain Research. JF - Behavioural Brain Research. SN - 0166-4328. ER - ...
Transgenic mouse models that overexpress APP develop senile plaques over time that resemble those found in human Alzheimers disease. These animals are a valuable tool toward understanding the physiology and pathology of senile plaques in living tissue and are ideal for evaluating therapeutics aimed at clearance of amyloid-β deposits in the brain. With the recent success using immunotherapy for prevention of amyloid-β deposits in these animals (Schenk et al., 1999; Bard et al., 2000), as well as clearance of existing plaques (Bacskai et al., 2001), this treatment seems very promising. Recent reports have also indicated that immunotherapy may have positive effects on behavioral deficits exhibited in transgenic mouse models (Janus et al., 2000; Morgan et al., 2000). These findings are important for predicting whether anti-amyloid therapies will prove beneficial not just in arresting deposition of amyloid-β but also in prevention of the associated dementia. Microglial cells were implicated in ...
Antibodies , OptimAb Antibodies , OptimAbᵀᴹ Beta-Amyloid 17-24 , Monoclonal Antibody, purified; Beta-Amyloid forms are deposited in the CNS of patients with Alzheimer s disease and Down s syndrome. Biochemical analysis of the amyloid peptides isolated from Alzheimer s disease brain indicates that Beta-Amyloid (1-42) is the principal species associated with senile plaque amyloids, while Beta-Amyloid (1-40) is more abundant in cerebrovascular amyloid deposits. Both result from the cleavage of Amyloid Precursor Protein (APP) by secretases. The mAb 4G8 reacts to the abnormally processed isoforms, as well as precursor forms.; Host: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),
Amyloid-β PET and CSF Aβ42 yield discordant results in 10-20% of memory clinic patients, possibly providing unique information. Although the predictive power of demographic, clinical, genetic, and imaging features for amyloid positivity has previously been investigated, it is unknown whether these features differentially predict amyloid-β status based on PET or CSF or whether this differs by disease stage. We included 768 patients (subjective cognitive decline (SCD, n = 194), mild cognitive impairment (MCI, n = 127), dementia (AD and non-AD, n = 447) with amyloid-β PET and CSF Aβ42 measurement within 1 year. Ninety-seven (13%) patients had discordant PET/CSF amyloid-β status. We performed parallel random forest models predicting separately PET and CSF status using 17 patient features (demographics, APOE4 positivity, CSF (p)tau, cognitive performance, and MRI visual ratings) in the total patient group and stratified by syndrome diagnosis. Thereafter, we selected features with the highest variable
Alzheimers disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18) in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress. We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP) and its processing products, its cleaving enzymes, involved in amyloidogenic processing of
Sigma-Aldrich offers abstracts and full-text articles by [Juliet A Moncaster, Roberto Pineda, Robert D Moir, Suqian Lu, Mark A Burton, Joy G Ghosh, Maria Ericsson, Stephanie J Soscia, Anca Mocofanescu, Rebecca D Folkerth, Richard M Robb, Jer R Kuszak, John I Clark, Rudolph E Tanzi, David G Hunter, Lee E Goldstein].
P05067: Amyloid beta A4 protein; ABPP; APPI; APP; Alzheimer disease amyloid protein; Cerebral vascular amyloid peptide; CVAP; PreA4; Protease nexin-II; PN-II; N-APP; Soluble APP-alpha; S-APP-alpha; Soluble APP-beta; S-APP-beta; C99; Beta-amyloid protein 42; Beta-APP42; Beta-amyloid protein 40; Beta-APP40; C83; P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59; Amyloid intracellular domain 59; AICD-59; AID(59); Gamma-CTF(59); Gamma-secretase C-terminal fragment 57; Amyloid intracellular domain 57; AICD-57; AID(57); Gamma-CTF(57); Gamma-secretase C-terminal fragment 50; Amyloid intracellular domain 50; AICD-50; AID(50); Gamma-CTF(50); C31; ...
Live discussion held 5 December 2001, noon-1 p.m. (EST).. Participants: Dick Lloyd, Sam Gandy, June Kinoshita, Richard Bowen, Nico Stanculescu, Seth Shaw, Mark Smith, Steve Fiander, Gunnar Gouras, Larry Tusick, Alan Lerner, Alexei R. Koudinov, Mike Shelanski, Rena Li, Gabrielle Strobel, Craig Atwood, and the mysterious Guest 2.. Note: The transcript has been edited for clarity and accuracy.. June: First, let me welcome you all to todays live discussion.. Sam Gandy: Thanks for organizing it, June.. June: I know that Richard Bowen has been eager to discuss some of the points in your discussion. Richard, would you like to ask the first question?. Richard L. Bowen: Yes, June: I wanted to know if Sam has looked at the ovariectomized mice and beta amyloid study, and have you had a chance to look at gonadotrophin levels?. Sam Gandy: We havent studied gonadotrophin levels under any circumstances. A paper on ovariectomy effects on Ab load in transgenic mice is in press at J. Neurochem. Co-authors are ...
Physical exercise has been suggested to reduce the risk of developing Alzheimers disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse model of AD did not affect levels of soluble amyloid beta (Aβ), synaptic proteins or cognitive function. In this follow-up study, we investigate whether running could impact other pathological aspects of the disease, such as insoluble Aβ levels, the neuroinflammatory response and non-cognitive behavioral impairments. We investigated the effects of 24 weeks of voluntary wheel running in female 5xFAD mice (n = 30) starting at 2-3 months of age, before substantial extracellular plaque formation. Running mice developed hindlimb clasping earlier (p = 0.009) compared to sedentary controls. Further, running exacerbated the exploratory behavior in Elevated plus maze
Dear Amyloid/Ageing subscribers: I began to study Alzheimers amyloid beta (Ab) protein in 1992, at the time when it was becoming clear that this protein exists normally in a soluble form (soluble Ab) and that it is not just a pathological protein. My research activities yielded an on-going project, devoted to understanding in more detail the normal biology of amyloid beta. Understanding the normal biology of Ab would answer the questions of why soluble Ab does not undergo fibrillogenesis in biological fluids but does polymerize into amyloid fibrils in the disease, and what the biological consequences of Ab deposition within the brain tissue are. This, in turn, would be crucial for understanding the pathophysiology of Alzheimers disease and for delineating pathologically grounded new approaches to therapy. My current postdoctoral position at NYU Medical Center just expired. Thus, to continue my research I have to find another position. I would be happy to continue my research as a part of your ...
Beta-amyloid is a protein fragment at the focus of research into the causes of Alzheimers disease. It is normally found in the brain but during the disease process, it forms small clumps known as oligomers, which are thought to be toxic to nerve cells. Eventually, beta-amyloid oligomers combine to form even larger structures known as fibrils, which then form amyloid plaques in the brain, one of the characteristic features of Alzheimers disease. Stephen Meredith, M.D., Ph.D., and colleagues have been studying the detailed molecular structure of beta-amyloid fibrils and working to identify what may trigger their development in Alzheimers disease. They have found that fibrils can have different structures from one person to the next, but that the fibrils found in different parts of the brain of a single person are generally the same. The researchers hypothesize that formation of an initial oligomer or fibril in one area of the brain may trigger the accumulation of other oligomers and subsequent ...
Proteolytic cleavage of amyloid-β-protein precursor (AβPP) by β- and γ-secretases results in production of the amyloid-β peptide (Aβ) that accumulates in the brains of sufferers of Alzheimers disease (AD). We have developed a monoclonal antibody, 2B
Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. GTP hydrolysis in protein synthesis: two for Tu?
Soluble β-amyloid peptide (βAP) is measured in biological fluids at very low concentrations, typically in the range from 0.1 ng/ml to 10 ng/ml. The measurement of βAP concentrations in animals or conditioned medium from cultured cells can be used for drug screening, where test compounds are administered to the animals or exposed to the cultured cells and the accumulation of βAP in the animal or culture medium observed. It has been found that elevated levels of βAP in body fluids, such as blood and cerebrospinal fluid, is associated with the presence of a βAP-related condition in a patient, such as Alzheimers Disease. Methods for diagnosing and monitoring βAP-related conditions comprise measuring the levels of βAP in such body fluids from a patient.
My research is focussed on Alzheimers Drug Discovery and compounds that modify amyloid fibril toxicity. I have discovered amyloid peptide interactions with the Kisspeptin, Kissorphin and Neuropeptide-FF peptides, which prevent the toxicity of the amyloid peptides in vitro. I discovered that endocannabinoids are neuroprotective against the Alzheimers Amyloid-beta peptide in vitro. I have characterized interactions between amyloid peptides and the enzymes Catalase and Cyclin-Dependent-Kinase-1.. ...
Alzheimers disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-ß plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimers disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-ß pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-ß deposition in the progression from ageing to Alzheimers disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20-93 years; 47 amyloid-ß-positive) and 20 amyloid-ß-positive patients with mild cognitive impairment or Alzheimers disease ...
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 ...
The rapidly rising prevalence and cost of Alzheimers disease in recent decades has made the imaging of amyloid-β deposits the focus of intense research. Several amyloid imaging probes with purported specificity for amyloid-β plaques are currently at
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.
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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.
Depression is one of the most common psychiatric diseases and the prevalence of depressive symptoms in women is almost twice compared to men, although the reasons of this gender difference are not fully understood yet. Recently, soluble amyloid beta (Aβ)1-42 peptide has been receiving great importance in the development of depression, also considering that depression is highly comorbid with Alzheimers disease and other neurodegenerative illnesses. The central role played by Aβ in the development of depressive-like symptoms in rodents has been evidenced in environmental rodent model of depression. Indeed, we have previously found that lifelong exposure to n-3 polyunsaturated fatty acids (PUFA) deficient diet in female rats at 8 weeks of life leads to depressive like- symptoms and higher susceptibility to stress associated with increased Aβ levels. In order to understand if such effects were maintained over time, rats were exposed to the same diet regimen until 6 or 21 weeks of life. We found ...
Its activity as an inhibitor of inflammation could counteracts reactive astrogliosis induced by beta-amyloid peptide, in a ... "Palmitoylethanolamide counteracts reactive astrogliosis induced by beta-amyloid peptide". Journal of Cellular and Molecular ... For instance during β-amyloid-induced neuroinflammation the deregulation of cannabinoid receptors and its endogenous ligands ... "Palmitoylethanolamide Protects Against the Amyloid-β25-35-Induced Learning and Memory Impairment in Mice, an Experimental Model ...
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/ ...
"Alzheimer's disease beta-amyloid peptides are released in association with exosomes". Proceedings of the National Academy of ... "Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting". Science. 320 (5875): 520-523. doi: ...
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 ...
2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation". Nat. Med. 10 (9): 959-65. doi: ...
Guo Q, Xie J (Feb 2004). "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4". ... Xie J, Guo Q (Jun 2004). "AATF protects neural cells against oxidative damage induced by amyloid beta-peptide". Neurobiology of ... "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4". The Journal of Biological ...
Nelson TJ, Alkon DL (2007). "Protection against beta-amyloid-induced apoptosis by peptides interacting with beta-amyloid". J ... It has been shown to interact with a number of proteins, such as beta-amyloid, protein elongation factor 1alpha, and otoferlin ... Kwok SC, Liu X, Mangel P, Daskal I (2006). "PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer ...
... 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- ...
This protein may be a target of neurotoxic beta-amyloid peptide, and may mediate cellular vulnerability to beta-amyloid peptide ... Beta-amyloid peptide has been established to be a causative factor in neuron death and the consequent diminution of cognitive ... Lee Y, Chang DJ, Lee YS, Chang KA, Kim H, Yoon JS, Lee S, Suh YH, Kaang BK (2003). "Beta-amyloid peptide binding protein does ... The protein encoded by this gene is a beta-amyloid peptide-binding protein. It contains a structural module related to that of ...
Alzheimer's disease is characterized by build-ups of aggregates of the peptide beta-amyloid. Apolipoprotein E enhances ... high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease". ... Gunzburg MJ, Perugini MA, Howlett GJ (December 2007). "Structural basis for the recognition and cross-linking of amyloid ... This may be caused by an interaction with amyloid. ... proteolytic break-down of this peptide, both within and between ...
"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 ...
He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R (2004). "Reticulon family members modulate BACE1 activity and amyloid-beta peptide ...
Cho S, Hu Y (2007). "Activation of 5-HT4 receptors inhibits secretion of beta-amyloid peptides and increases neuronal survival ...
"S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by beta-amyloid peptide". Proceedings of the ...
2005). "Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against beta-amyloid peptide neurotoxicity". ... A scorpion venom peptide was found to help with arthritis in vitro. Various fungi are used in TCM. Some may have scientifically ... Lee DG, Jung HJ, Woo ER (September 2005). "Antimicrobial property of (+)-lyoniresinol-3alpha-O-beta-D-glucopyranoside isolated ...
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 ...
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 ...
The mutation occurs in the gene which encodes beta amyloid. Amyloid is one of the peptides which accumulate in the brains of ... "A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid". Nature Genetics. 1 ( ... The idea that amyloid could cause the disease influenced scientific research until this day. Many experimental treatments are ... As a consequence, the mice can develop amyloid plaques at around 13 months old. It is thought that the Swedish mutation causes ...
"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 ...
Buildup of beta amyloid (Aβ) peptides is shown to cause and/or trigger Alzheimer's disease. Aβ interferes with BDNF-induced ... which encodes a protein that is necessary for the last step of the sequential proteolytic processing of amyloid precursor ...
... augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proceedings of the National Academy of Sciences USA. ... as well as reducing levels of amyloid precursor protein and amyloid beta, which are commonly used biomarkers for the ...
"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) ...
Milner-White, EJ; Watson (2006). "Amyloid formation may involve alpha- to beta sheet interconversion via peptide plane flipping ... Peptide nests are small anion-binding molecular features of proteins and peptides. Each consists of the main chain atoms of ... A few have so little that the concavity is lost; these peptides often bind cations via their main chain CO groups, instead of ... Most PDZ domains have an RL nest at the beginning of the first beta-strand, with the function of recognizing the carboxylate ...
Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids ... A new beta cell secretory product related to islet amyloid deposits". J. Biol. Chem. 265 (8): 4173-4176. PMID 2407732. Breimer ... A new beta cell secretory product related to islet amyloid deposits". J. Biol. Chem. 265 (8): 4173-6. PMID 2407732. This ... beta type InterPro: IPR002163 CALCA; CALCB; IAPP Breimer LH, Zaidi M, MacIntyre I (1988). "Peptides from the calcitonin genes: ...
"An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta -sheet structure for amyloid". Proceedings of ... 2008 in recognition of his contributions in unfolding the structure of amyloid fibrils. The award was presented to him at a ...
"Transgenic tomatoes expressing human beta-amyloid for use as a vaccine against Alzheimer's disease". Biotechnology letters. 30 ... The plant peptide hormone, systemin was first identified in tomato plants and genetic modification has been used to demonstrate ... "Expression of a synthesized gene encoding cationic peptide cecropin B in transgenic tomato plants protects against bacterial ...
lt has as its unique component the islet beta-cell peptide islet amyloid polypeptide (IAPP), which is eo-secreted with insulin ... In contrast to MAb4A5 polyclonal rabbitiAPP antisera label beta cells close to amyloid only weakly, but label strongly IAPP in ... have revealed a paradoxical and unexplained lack of IAPP immunoreactivity in beta cells close to amyloid in spite of the ... irrespective of presence of amyloid in these islets. The finding may indicate that the formation of first islet amyloid occurs ...
P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving ... Amyloid beta (Abeta) peptides are hypothesized to cause the initiation and progression of AD based on pathologic data from AD ... P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving ... P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving ...
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 ...
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, ...
... 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 ...
Acceleration of amyloid beta-peptide aggregation by physiological concentrations of calcium.. Isaacs AM1, Senn DB, Yuan M, ... Alzheimer disease is characterized by the accumulation of aggregated amyloid beta-peptide (Abeta) in the brain. The ... Using this approach, we directly compared the neurotoxicity of protofibrils and mature amyloid fibrils and demonstrate that ... the site at which amyloid plaque deposition occurs. In the absence of calcium, protofibrils can remain stable in vitro for ...
A beta) peptide is a cytotoxic peptide implicated in the pathology of Alzheimers disease (AD). Catalase and the endoplasmic ... reticulum A beta binding dehydrogenase (ERAB) are both inhibited by characterized fragments of the A beta peptide. In order to ... The amyloid-beta (A beta) peptide is a cytotoxic peptide implicated in the pathology of Alzheimers disease (AD). Catalase and ... Identification of amyloid-beta binding sites using an antisense peptide approach Neuroreport. 2001 Aug 8;12(11):2561-6. doi: ...
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 ...
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 ...
... Mark A. Lovell,1,2 Erin ... and Effects on Amyloid Beta Peptide Production," Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 787805, 9 ...
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 ...
... are peptides known as amyloid beta-peptides (Abeta), which derive from the proteolitic cleavage of the amyloid precursor ... are peptides known as amyloid beta-peptides (Abeta), which derive from the proteolitic cleavage of the amyloid precursor ... Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion ... Solution structure of the Alzheimers disease amyloid beta-peptide (1-42). *DOI: 10.2210/pdb1IYT/pdb ...
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, ...
... amyloid peptides to assist your research on neuroscience. ... is proud to manufacture high quality and comprehensive beta(β) ... Beta Amyloid Peptides. Beta-amyloid is a peptide that forms amyloid plaques in the brains of Alzheimers disease (AD) patients ... Beta amyloid peptide consists of 43 amino acids. It is created via the enzymatic digestion of amyloid precursor protein (APP) ... GenScripts FlexPeptide peptide synthesis platform allows us to synthesize a comprehensive array of human and rat beta amyloid ...
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 ...
In this study, we demonstrate that the pro-inflammatory protein S100A9 interacts with the A1-40 peptide and promotes the ... This interaction also results in reduced S100A9 cytotoxicity by the binding of S100A9 toxic species to A1-40 amyloid structures ... These results suggest that secretion of S100A9 during inflammation promotes the formation of amyloid plaques. By acting as a ... Amyloid plaques Is the Subject Area "Amyloid plaques" applicable to this article? Yes. No. ...
... 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 ...
... activity relationship for beta-amyloid, aggregation properties of an overlapping series of synthetic beta-amyloid peptides ( ... Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. CJ Pike, D Burdick, AJ ... Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state ... Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state ...
Synthetic beta-amyloid peptides (beta APs) corresponding to amino acids 1-38 or 25-35 of the beta-amyloid protein enhanced ... beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. MP ... beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity ... beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity ...
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 ...
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 ...
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 ...
... peptides. The present paper describes a novel and easy-to-run capillary electrophoresis with laser-induced fluorescence ... to the separation of Aβ fibrillar aggregates of different sizes and showed that highly concentrated solutions of Aβ peptides ... Alzheimers disease is characterized by the accumulation of brain amyloid plaques composed of aggregates of amyloid β (Aβ) ... Advances and Pitfalls in the Capillary Electrophoresis Analysis of Aggregates of Beta Amyloid Peptides. Luc Denoroy 1,* and ...
The present study examined the relationship between amyloid beta (Aß)-peptide aggregation state and neurotoxicity in vitro ... Differential effects of amyloid-beta peptide aggregation status on in vivo retinal neurotoxicity HR Watts1, PJB Anderson1, D ... Differential effects of amyloid-beta peptide aggregation status on in vivo retinal neurotoxicity. ... Abstract: The present study examined the relationship between amyloid beta (Aβ)-peptide aggregation state and neurotoxicity in ...
... and beta(1-40), giving rise to a new excitation (ex) (absorption) maximum at 450 nm and enhanced emission (em) at 482 nm, as ... associates rapidly with aggregated fibrils of the synthetic beta/A4-derived peptides beta(1-28) ... Thioflavine T interaction with synthetic Alzheimers disease beta-amyloid peptides: detection of amyloid aggregation in ... Thioflavine T (ThT) associates rapidly with aggregated fibrils of the synthetic beta/A4-derived peptides beta(1-28) and beta(1- ...
  • These studies showed that all three BACE1 inhibitors decreased brain Abeta1-40 in P-gp KO mice, demonstrating that P-gp is a major limitation for development of BACE1 inhibitors to test the amyloid hypothesis. (geoscience.net)
  • Martins AH, Zayas-Santiago A, Ferrer-Acosta Y, Martinez-Jimenez SM, Zueva L, Diaz-Garcia A, Inyushin M. Accumulation of Amyloid Beta (Aβ) Peptide on Blood Vessel Walls in the Damaged Brain after Transient Middle Cerebral Artery Occlusion. (mdpi.com)
  • To better understand the link between NE, chronic stress and aberrant A42 accumulation, we used mice that conditionally overexpress corticotropin releasing factor (CRF OE) to determine if perturbation of the stress-signaling axis would alter A[beta]42 levels or distribution. (drexel.edu)
  • GenScript provides blocking peptides for most of our antibodies. (genscript.com)
  • Finally, the beta APs made neurons more vulnerable to neurofibrillary tangle-like antigenic changes induced by EAAs or calcium ionophore (i.e., increased staining with tau and ubiquitin antibodies). (jneurosci.org)
  • The established method employed murine monoclonal and rabbit polyclonal antibodies and was capable of yielding well-reproducible peaks of high intensity with low background signal intensities corresponding to various A beta forms. (diva-portal.org)
  • 14. The immunoassay kit of claim 11, wherein the rodent amyloid Peptide in the sample selected from Aβ 1-40 and Aβ 1-42 are captured with solid-phase antibody carriers having said antibodies immobilized thereon. (patentsencyclopedia.com)
  • Catalase and the endoplasmic reticulum A beta binding dehydrogenase (ERAB) are both inhibited by characterized fragments of the A beta peptide. (nih.gov)
  • GenScript's FlexPeptide peptide synthesis platform allows us to synthesize a comprehensive array of human and rat beta amyloid peptide fragments covering stretches of its amino acid sequence. (genscript.com)
  • 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)
  • The focus of this project is two-fold: examining the native structures of three different fragments of the beta-amyloid (A[beta]) peptide, and attempting to overcome some of the difficulties encountered in such an examination. (umsystem.edu)
  • The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. (rsc.org)
  • Many experimental measurements require an accurate estimate of peptide concentration, which can prove to be particularly problematic for peptides such as A[beta] that are not easily soluble in aqueous solvents. (umsystem.edu)
  • rPeptide's recombinant beta-amyloid peptides are prepared as a very soluble (proprietary) fusion, to significantly reduce the non-specific binding in an impure prep. (blogspot.com)
  • 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. (google.com)
  • 7. A method for reducing soluble β-amyloid peptide (βAP) in a patient suffering from a β-amyloid peptide-related disease, said method comprising administering to the patient an amount of a small molecule effective to reduce the amount of βAP present in a body fluid of the patient. (google.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)
  • Cosmetic Peptides such as Lysine and Cysteine Peptide are used for DPRA (Direct Peptide Reactivity Assay) for Skin Sensitization Testing. (jpt.com)
  • In the present study, both laser light treatment and soybean isoflavones treatment showed the ability to suppress A[beta]-induced oxidative stress and inflammation response. (umsystem.edu)
  • The second mechanism by which βSBPs produce their effects is that βSBPs can bind to the central hydrophobic cluster, via hydrogen bridges in a manner rendering the βSBP sitting in the central hydrophobic region of Aβ on the plane of amyloid dimmer , and thereby destabilizing the interaction between Aβ monomers and/or oligomers that is necessary for fibril stability. (remedypublications.com)