Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type.Viral Structural Proteins: Viral proteins that are components of the mature assembled VIRUS PARTICLES. They may include nucleocapsid core proteins (gag proteins), enzymes packaged within the virus particle (pol proteins), and membrane components (env proteins). These do not include the proteins encoded in the VIRAL GENOME that are produced in infected cells but which are not packaged in the mature virus particle,i.e. the so called non-structural proteins (VIRAL NONSTRUCTURAL PROTEINS).Serum Amyloid A Protein: An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.Erythrocyte Aggregation: The formation of clumps of RED BLOOD CELLS under low or non-flow conditions, resulting from the attraction forces between the red blood cells. The cells adhere to each other in rouleaux aggregates. Slight mechanical force, such as occurs in the circulation, is enough to disperse these aggregates. Stronger or weaker than normal aggregation may result from a variety of effects in the ERYTHROCYTE MEMBRANE or in BLOOD PLASMA. The degree of aggregation is affected by ERYTHROCYTE DEFORMABILITY, erythrocyte membrane sialylation, masking of negative surface charge by plasma proteins, etc. BLOOD VISCOSITY and the ERYTHROCYTE SEDIMENTATION RATE are affected by the amount of erythrocyte aggregation and are parameters used to measure the aggregation.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.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.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.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.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.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.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.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)Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).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.alpha-Crystallin B Chain: One of the alpha crystallin subunits. In addition to being expressed in the lens (LENS, CRYSTALLINE), alpha-crystallin B chain has been found in a variety of tissues such as HEART; BRAIN; MUSCLE; and KIDNEY. Accumulation of the protein in the brain is associated with NEURODEGENERATIVE DISEASES such as CREUTZFELDT-JAKOB SYNDROME and ALEXANDER DISEASE.Inclusion Bodies: A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed)Congo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.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)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.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).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, 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.Viral Proteins: Proteins found in any species of virus.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)Serum Amyloid P-Component: Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.Amyloid Neuropathies: Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.HSP40 Heat-Shock Proteins: A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.ThiazolesMicroscopy, 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.Kinetics: The rate dynamics in chemical or physical systems.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Proteostasis Deficiencies: Disorders caused by imbalances in the protein homeostasis network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.Scattering, Radiation: The diversion of RADIATION (thermal, electromagnetic, or nuclear) from its original path as a result of interactions or collisions with atoms, molecules, or larger particles in the atmosphere or other media. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Hydrophobic and Hydrophilic Interactions: The thermodynamic interaction between a substance and WATER.Physical Phenomena: The entities of matter and energy, and the processes, principles, properties, and relationships describing their nature and interactions.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.alpha-Crystallins: A subclass of crystallins that provides the majority of refractive power and translucency to the lens (LENS, CRYSTALLINE) in VERTEBRATES. Alpha-crystallins also act as molecular chaperones that bind to denatured proteins, keep them in solution and thereby maintain the translucency of the lens. The proteins exist as large oligomers that are formed from ALPHA-CRYSTALLIN A CHAIN and ALPHA-CRYSTALLIN B CHAIN subunits.Nerve Tissue ProteinsProtein 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.Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions.HSP70 Heat-Shock Proteins: A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.alpha-Crystallin A Chain: One of the subunits of alpha-crystallins. Unlike ALPHA-CRYSTALLIN B CHAIN the expression of ALPHA-CRYSTALLIN A CHAIN is limited primarily to the lens (LENS, CRYSTALLINE).Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.Protein Renaturation: The reconstitution of a protein's activity following denaturation.Fractionation, Field Flow: Separation of molecules and particles by a simultaneous action of carrier liquid flow and focusing field forces (electrical, sedimentation, or thermal), without a stationary phase.Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Huntington Disease: A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.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).Crystallins: A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses.Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Unfolding: Conformational transitions of the shape of a protein to various unfolded states.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)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.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.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.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.Hot Temperature: Presence of warmth or heat or a temperature notably higher than an accustomed norm.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.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.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.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.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.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)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.Amyotrophic Lateral Sclerosis: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)Synucleins: A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.Lens, Crystalline: A transparent, biconvex structure of the EYE, enclosed in a capsule and situated behind the IRIS and in front of the vitreous humor (VITREOUS BODY). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the CILIARY BODY is crucial for OCULAR ACCOMMODATION.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.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.Poly(A)-Binding Protein II: A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.Capsid Proteins: Proteins that form the CAPSID of VIRUSES.gamma-Crystallins: A subclass of crystallins that found in the lens (LENS, CRYSTALLINE) of VERTEBRATES. Gamma-crystallins are similar in structure to BETA-CRYSTALLINS in that they both form into a Greek key-like structure. They are composed of monomeric subunits.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.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.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.Heat-Shock Proteins, Small: A family of low molecular weight heat-shock proteins that can serve as MOLECULAR CHAPERONES.Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Physics: The study of those aspects of energy and matter in terms of elementary principles and laws. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)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.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.Virus Assembly: The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Preservatives, Pharmaceutical: Substances added to pharmaceutical preparations to protect them from chemical change or microbial action. They include ANTI-BACTERIAL AGENTS and antioxidants.Platelet Membrane Glycoproteins: Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).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.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Muscular Dystrophy, Oculopharyngeal: An autosomal dominant hereditary disease that presents in late in life and is characterized by DYSPHAGIA and progressive ptosis of the eyelids. Mutations in the gene for POLY(A)-BINDING PROTEIN II have been associated with oculopharyngeal muscular dystrophy.Cataract: Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)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.Multiprotein Complexes: Macromolecular complexes formed from the association of defined protein subunits.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Thromboxane B2: A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.Platelet Function Tests: Laboratory examination used to monitor and evaluate platelet function in a patient's blood.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Anilino Naphthalenesulfonates: A class of organic compounds which contain an anilino (phenylamino) group linked to a salt or ester of naphthalenesulfonic acid. They are frequently used as fluorescent dyes and sulfhydryl reagents.Citrate (si)-Synthase: Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.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.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Biopolymers: Polymers synthesized by living organisms. They play a role in the formation of macromolecular structures and are synthesized via the covalent linkage of biological molecules, especially AMINO ACIDS; NUCLEOTIDES; and CARBOHYDRATES.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Lubrication: The application of LUBRICANTS to diminish FRICTION between two surfaces.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Rubella virus: The type (and only) species of RUBIVIRUS causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis.Trinucleotide Repeat Expansion: An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.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.Chemical Precipitation: The formation of a solid in a solution as a result of a chemical reaction or the aggregation of soluble substances into complexes large enough to fall out of solution.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)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.Light: That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.Solutions: The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed)Antibodies, Monoclonal: Antibodies produced by a single clone of cells.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Sindbis Virus: The type species of ALPHAVIRUS normally transmitted to birds by CULEX mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. Serotypes (differing by less than 17% in nucleotide sequence) include Babanki, Kyzylagach, and Ockelbo viruses.Bacterial Proteins: Proteins found in any species of bacterium.Peptide Termination Factors: Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent.Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1.Signal 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.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Luminescent Proteins: Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.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.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.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.Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with LIDOCAINE injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring.Genes, Viral: The functional hereditary units of VIRUSES.Heat-Shock Response: A constellation of responses that occur when an organism is exposed to excessive heat. Responses include synthesis of new proteins and regulation of others.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Horses: Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest.Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)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).Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.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.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Heredodegenerative Disorders, Nervous System: Inherited disorders characterized by progressive atrophy and dysfunction of anatomically or physiologically related neurologic systems.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.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.Protein PrecursorsPrion Diseases: A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Water: A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)ChymotrypsinogenBiophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Lactoglobulins: Globulins of milk obtained from the WHEY.Myoviridae: A family of BACTERIOPHAGES and ARCHAEAL VIRUSES which are characterized by complex contractile tails.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.

*Alpha-synuclein

... involved in protein aggregation Residues 96-140: a highly acidic and proline-rich region which has no distinct structural ... "The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous ... Ono K, Takahashi R, Ikeda T, Yamada M (Sep 2012). "Cross-seeding effects of amyloid β-protein and α-synuclein". Journal of ... The central panel in the figure to the right shows the major pathway for protein aggregation. Monomeric α-synuclein is natively ...

*Amyloid

Irvine GB, El-Agnaf OM, Shankar GM, Walsh DM (2008). "Protein aggregation in the brain: the molecular basis for Alzheimer's and ... Meier, BH; Riek, R; Bockmann, A (2017). "Emerging Structural Understanding of Amyloid Fibrils by Solid-State NMR". Trends ... but often this can cause trouble because epitopes can be concealed in the amyloid fold; in general, an amyloid protein ... Inclusion Bodies Contain Amyloid-Like Structure at SciVee Amyloid Cascade Hypothesis Stanford University Amyloid Center Amyloid ...

*Alpha sheet

PMID 9449354 Xu S. Aggregation drives "misfolding" in protein amyloid fiber formation. Amyloid 2007 Jun;14(2):119-31. PMID ... Malinchik, S. B., Inouye, H., Szumowski, K. E. & Kirschner, D. A. (1998). Structural analysis of Alzheimer's beta(1-40) amyloid ... all of which are associated with protein misfolding disease. For example, amyloid beta is a major component of amyloid plaques ... This suggests a possible mechanism by which alpha sheet may promote amyloid aggregation; the peptide bond has a relatively ...

*Sheena Radford

Radford's research investigates protein folding, protein aggregation and amyloid disease. Radford was elected a Fellow of the ... subscription required) Folding proteins - from Astbury to Amyloid and Ageing on YouTube Astbury Centre for Structural Molecular ... unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis". Nature. 385 (6619): 787-93. doi: ... "Pulling geometry defines the mechanical resistance of a β-sheet protein". Nature Structural Biology. 10 (9): 731. doi:10.1038/ ...

*Calpastatin

The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. ... and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous ... membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. ... Calpastatin is a protein that in humans is encoded by the CAST gene. The protein encoded by this gene is an endogenous calpain ...

*Neurodegeneration

Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that ... Hashimoto M, Rockenstein E, Crews L, Masliah E (2003). "Role of protein aggregation in mitochondrial dysfunction and ... Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein". Biochem. Soc. Trans ...

*Protein folding

The structural stability of these fibrillar assemblies is caused by extensive interactions between the protein monomers, formed ... van den Berg B, Ellis RJ, Dobson CM (December 1999). "Effects of macromolecular crowding on protein folding and aggregation". ... Soto C, Estrada L, Castilla J (March 2006). "Amyloids, prions and the inherent infectious nature of misfolded protein ... Home Foldit computer game Potential energy of protein Protein dynamics Protein misfolding cyclic amplification Protein ...

*G. Marius Clore

The latter includes an atomic-resolution view of the dynamics of the amyloidaggregation process. Clore is one of the most ... and for developing NMR-based methods to study rare conformational states in protein-nucleic acid and protein-protein ... G. Marius Clore FRSC (born June 6, 1955) is a British-born, American molecular biophysicist and structural biologist. He was ... CS1 maint: Uses authors parameter (link) Clore GM (2000). "Accurate and rapid docking of protein-protein complexes on the basis ...

*Jayant B. Udgaonkar

His current work focuses on formation of amyloid fibrils and his research has shown multiple pathways of aggregation in the ... Protein folding Amyloid Barstar Acetylcholine receptor India portal Biology portal Please see Selected bibliography section ... A former guest editor of the Current Opinion in Structural Biology of Elsevier (2013 and 2015) and a former editorial board ... Cooperativity in protein folding/unfolding reactions". Protein Science. 25: 1924-1941. doi:10.1002/pro.3015. Rama Reddy ...

*Beta sheet

... association between proteins that might lead to aggregation and amyloid formation. A very simple structural motif involving β- ... Tertiary Protein Structure and Folds: section 4.3.2.1. From Principles of Protein Structure, Comparative Protein Modelling, and ... see amyloid plaque) can form β-sheet-rich oligomeric structures associated with pathological states. The amyloid β protein's ... See sections II B and III C, D in Richardson JS (1981). Anatomy and Taxonomy of Protein Structures. Advances in Protein ...

*Chemical biology

A common form of aggregation is long, ordered spindles called amyloid fibrils that are implicated in Alzheimer's disease and ... Also of interest are protein-protein interactions, cellular distribution of proteins and understanding protein activity. ... While there is no published in vivo data on compounds of this type, the structural data acquired from in vitro studies have ... protein-protein interactions, protein synthesis and turnover, and enzyme activity, among others. Three general approaches for ...

*Biochemistry of Alzheimer's disease

Amyloid-beta, also written Aβ, is a short peptide that is a proteolytic byproduct of the transmembrane protein amyloid ... AD is also considered a tauopathy due to abnormal aggregation of the tau protein, a microtubule-associated protein expressed in ... Danielsson J, Andersson A, Jarvet J, Gräslund A (2006). "15N relaxation study of the amyloid beta-peptide: structural ... AD has been identified as a protein misfolding disease due to the accumulation of abnormally folded amyloid beta protein in the ...

*Robustness (evolution)

Fink, AL (1998). "Protein aggregation: folding aggregates, inclusion bodies and amyloid". Folding & Design. 3 (1): R9-23. doi: ... Protein mutation tolerance is the product of two main features: the structure of the genetic code and protein structural ... Monsellier, E; Chiti, F (Aug 2007). "Prevention of amyloid-like aggregation as a driving force of protein evolution". EMBO ... Proteins are resistant to mutations because many sequences can fold into highly similar structural folds. A protein adopts a ...

*Neutral network (evolution)

Fink, AL (1998). "Protein aggregation: folding aggregates, inclusion bodies and amyloid". Folding & Design. 3 (1): R9-23. doi: ... Proteins are resistant to mutations because many sequences can fold into highly similar structural folds. A protein adopts a ... Monsellier, E; Chiti, F (Aug 2007). "Prevention of amyloid-like aggregation as a driving force of protein evolution". EMBO ... Tokuriki, N; Tawfik, DS (Oct 2009). "Stability effects of mutations and protein evolvability". Current Opinion in Structural ...

*Jeffery W. Kelly

Besides studying the structural and energetic basis underlying protein folding, his laboratory also studies the etiology of ... the idea that active transthyretin aggregation causes the loss of post-mitotic tissue in this degenerative amyloid disease. ... His research focuses on understanding protein folding, misfolding and aggregation and on developing both chemical and ... cellular protein homeostasis or proteostasis capacity has the potential to alleviate protein misfolding and aggregation ...

*Insulin-degrading enzyme

... amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo". Proceedings of the National Academy ... The calculated theoretical pI of this protein isoform is 6.26. Structural studies of IDE by Shen et al. have provided insight ... preventing aggregation, and, ideally, preventing the neuronal loss that leads to disease symptoms. IDE was first identified by ... Aβ is a byproduct generated as the result of proteolytic processing of the amyloid precursor protein (APP) by proteases ...

*Athene Donald

... notably protein aggregation. Further details of her research can be found in the citation for the Faraday Medal she was awarded ... Krebs, M.R.H.; Bromley, E.H.C.; Donald, A.M. (2005). "The binding of thioflavin-T to amyloid fibrils: Localisation and ... Structural changes during cooking, with the amylopectin molecule imaginatively treated as a side chain liquid crystalline ... The misfolding of proteins forming amyloid fibrils is well recognized in the aetiology of many diseases, particularly those of ...

*Proteopathy

Lundmark K, Westermark GT, Olsen A, Westermark P (2005). "Protein fibrils in nature can enhance amyloid protein A amyloidosis ... and the aggregation of superoxide dismutase-1 (SOD1), polyglutamine, and TAR DNA-binding protein-43 (TDP-43). In all of these ... possibly because of structural complementarity of the protein molecules. For example, AA amyloidosis can be stimulated in mice ... actually is rich in protein. Subsequent research has shown that many different proteins can form amyloid, and that all amyloids ...

*TARDBP

TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa), is a protein that in humans is encoded by ... Moreover, zinc could bind to RNA binding domain of TDP-43 and induce the formation of amyloid-like aggregates in vitro. A hyper ... Kuo PH, Doudeva LG, Wang YT, Shen CK, Yuan HS (2009). "Structural insights into TDP-43 in nucleic-acid binding and domain ... The N-terminal domain, which contributes importantly to the aggregation of the C-terminal region, has a novel structure with ...

*Carol V. Robinson

... unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis". Nature. 385 (6619): 787-93. Bibcode: ... spectrometry and pioneering gas phase structural biology by probing the structure and reactivity of single proteins and protein ... Marsh, J. A.; Hernández, H; Hall, Z; Ahnert, S. E.; Perica, T; Robinson, C. V.; Teichmann, S. A. (2013). "Protein complexes are ... Miranker, A; Robinson, C. V.; Radford, S. E.; Aplin, R. T.; Dobson, C. M. (1993). "Detection of transient protein folding ...

*Amyloid beta

Intra-cellular deposits of tau protein are also seen in the disease, and may also be implicated, as has aggregation of alpha ... "Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils". Nature Structural & Molecular Biology. 17 (5): ... Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ... and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). Aβ circulates in plasma, ...

*Familial amyloid cardiomyopathy

... results from the aggregation and deposition of mutant and wild-type transthyretin (TTR) protein in the heart. TTR amyloid ... clinicopathologic and structural considerations. Amyloid 10 Suppl 1, 48-54. Falk, R. H. & Elkayam, U. (2010). Cardiomyopathy: ... Familial Amyloid Cardiomyopathy (FAC), or Transthyretin Amyloid Cardiomyopathy (ATTR-CM) ... Prevention of transthyretin amyloid disease by changing protein misfolding energetics. Science 299, 713-6. Coelho, T. (1996). ...

*High-density lipoprotein

It is the densest because it contains the highest proportion of protein to lipids. Its most abundant apolipoproteins are apo A- ... In the stress response, serum amyloid A, which is one of the acute-phase proteins and an apolipoprotein, is under the ... 2008). "Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor". PNAS. 105 (35): 13045- ... and platelet aggregation. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is ...

*Hydrophobic collapse

"Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world". Biochimica et ... The formation of amyloid fibrils, insoluble aggregates of hydrophobic protein can lead to a myriad of diseases including ... ISBN 978-0470-54784-7. Gilmanshin R, Dyer RB, Callender RH (1997). "Structural heterogeneity of the various forms of ... Correct protein folding is integral to proper functionality within biological systems. Hydrophobic collapse is one of the main ...

*P3 peptide

... generates from the 17-40 or 17-42 sequence of the amyloid precursor protein (APP), which is a type I integral ... Synthesis of disubstituted amino acids and peptide inhibitors of amyloid beta aggregation (MS Thesis). Louisiana State ... As a consequence, p3 peptide structural determinants can assemble into fibrils, but no oligomeric forms have been identified. ... and γ-secretase cleavage from the amyloid precursor protein (APP). It is known to be the major constituent of diffuse plaques ...
Westwell-Roper, C.Y.; Chehroudi, C.A.; Denroche, H.C.; Courtade, J.A.; Ehses, J.A.; Verchere, C.Bruce., 2015: IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice
If you have a question about this talk, please contact Dr Georg Krainer.. Many bacteria produce functional amyloid, i.e. proteins which are secreted through dedicated export systems and self-assemble on the bacterial surface, often with the help of nucleator proteins. These amyloid proteins serve a diversity of purposes, but the most prominent one appears to be structural stability; for example, overexpression of the amyloid-forming protein FapC in Pseudomonas species strengthens bacterial biofilm against mechanical insults, increases hydrophobicity and protects against desiccation. Similar properties are ascribed to the curli-forming protein CsgA from E. coli. Unlike pathological amyloid, functional amyloid has been under evolutionary pressure to self-assemble efficiently (i.e. in a single "fast track") to very stable ...
Islet amyloid is the most common characteristic feature of the islets in type 2 diabetes, being found in up to 90% of diabetic patients at post-mortem. lt has as its unique component the islet beta-cell peptide islet amyloid polypeptide (IAPP), which is eo-secreted with insulin. Because all human subjects produce and secrete the amyloidogenic form of IAPP, yet not all develop islet amyloid, some other factors must be involved in islet amyloid formation. The aim of the research presented in this thesis was to study factors of importance for the IAPP amyloidogenesis in type 2 diabetes. We developed a mouse monoclonal antibody to raVmouse IAPP (MAb4A5). MAb4A5 shows reactivity with IAPP in different species without detecting its close relative CGRP. In the pancreatic islets from patients with type 2 diabetes and diabetic cat, MAb4A5 labels immunohistochemically cellular IAPP but not IAPP in islet ...
We have revisited the well-studied heat and acidic amyloid fibril formation pathway (pH 1.6, 65 °C) of hen egg-white lysozyme (HEWL) to map the barriers of the misfolding and amyloidogenesis pathways. A comprehensive kinetic mechanism is presented where all steps involving protein hydrolysis, fragmentation, assembly and conversion into amyloid fibrils are accounted for. Amyloid fibril formation of lysozyme has multiple kinetic barriers. First, HEWL unfolds within minutes, followed by irreversible steps of partial acid hydrolysis affording a large amount of nicked HEWL, the 49-101 amyloidogenic fragment and a variety of other species over 5-40 h. Fragmentation forming the 49-101 fragment is a requirement for efficient amyloid fibril formation, indicating that it forms the rate-determining nucleus. Nicked full-length HEWL is recruited efficiently into amyloid fibrils in the ...
Ellibs Ebookstore - Ebook: Computational Modelling of the Human Islet Amyloid Polypeptide - Author: Skeby, Katrine Kirkeby - Price: 138,35€
Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014. Summary. Global Markets Direct s, Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, H1 2014, provides an overview of the indication s therapeutic pipeline. This report provides information on the therapeutic development for Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease), complete with latest updates, and special features on late-stage and discontinued projects. It also reviews key players involved in the therapeutic development for Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease). Familial Amyloid Polyneuropathy (Transthyretin Amyloidosis, Corino de Andrades Disease) - Pipeline Review, Half ...
Our primary objective was to establish whether metformin or sitagliptin alone and in combination favorably modified disease progression in the HIP rat model of type 2 diabetes. Although loss of β-cell mass in the HIP rat was slowed by this combination therapy, unexpected adverse actions on the exocrine pancreas were also observed.. Metformin has been shown to delay type 2 diabetes onset in humans (13). Because enhanced insulin sensitivity through lifestyle changes also delays diabetes (13), at least part of the protective effect of metformin may be mediated by metformins actions to enhance hepatic insulin sensitivity through its actions on AMP-activated kinase (33). Metformin decreased β-cell apoptosis in isolated human islets from patients with type 2 diabetes (34). In the current study, metformin was more effective than sitagliptin in reducing β-cell apoptosis in the high-fat diet -fed HIP rat. Although sitagliptin alone also suppressed β-cell apoptosis, there was no added benefit of ...
Amyloid formation is inherent property of proteins which under certain circumstances can become a pathologic feature of a group of diseases called amyloidosis. There are about 30 known human amyloidosis and more than 27 identified proteins involved in these pathologies. Besides these proteins, there are a growing number of proteins non-related to diseases shown to form amyloid-like structures in vitro, which make them excellent tools for studying amyloid formation mechanisms, physicochemical properties of different amyloid species and the nature of their influence on tissues and cells. It is important to understand the mechanisms by which amyloids interact with different types of cells, as the leading hypothesis in amyloid field suggests that amyloids and especially their intermediate states ...
The 37-residue human islet amyloid polypeptide (hIAPP or amylin) self-assembles into fibers, the assembly of which has been associated with the disease mechanism of type II diabetes. Infrared spectroscopy in conjunction with isotope labeling is proving to be a powerful tool for studying the aggregation process of hIAPP and other amyloid forming proteins with residue specific structure and kinetic information, but the relationship between the spectroscopic observables and the structure is not fully established. We report a detailed analysis of the linear and 2D IR spectra of hIAPP fibers isotope labeled at seven different residue positions. The features of the 2D IR spectra, including the frequencies, linewidths, intensities, and polarization dependence of the diagonal and cross-peaks, rely heavily on the position of the isotope labeled residue. In order to understand how these measured parameters depend on fiber secondary ...
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 ...
The structures of amyloid fibrils and oligomers represent a vast frontier, of yet unknown scope. The fibrils and aggregates that amyloidogenic peptides and proteins form are rich in β-sheets, and their structures are tremendously important in amyloid diseases. Many structures of amyloid fibrils have been discovered by solid-state NMR spectroscopy of amyloidogenic peptides and proteins and by X-ray crystallography of smaller fragments.1-4 Studying amyloid oligomer structures at high resolution is challenging, because amyloid oligomers are heterogeneous and dynamic, forming various species of different sizes and morphologies. Although a few structures of amyloid oligomers have been discovered in the last decade, there are not enough to provide a full understanding of amyloid assemblies.5-7 Our laboratory has pioneered the use ...
The use of small carbohydrates that stabilize proteins from misfolding is important from pharmaceutical point of view. We have investigated the role of small isomeric amino sugars on the in vitro aggregation of insulin amyloid. Using mass spectrometry, we screened 6 isomeric aminosugars for their role on inhibition of insulin amyloid formation and the results were compared with transmission electron microscopy imaging. We found that three N-acetylamino sugars promote insulin fibril formation. Among three isomeric aminosugars studied, only galactosamine showed few fibrils whereas other two isomers showed enhanced fibrils. The results demonstrated here may contribute to future designing of small amine derivatised galactose sugars as amyloid inhibitors and understanding their action ...
Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of beta-cells of the pancreatic islets of Langerhans. It is a regulatory peptide with putative function both locally in the islets, where it inhibits insulin and glucagon secretion, and at distant targets. It has binding sites in the brain, possibly contributing also to satiety regulation and inhibits gastric emptying. Effects on several other organs have also been described. IAPP was discovered through its ability to aggregate into pancreatic islet amyloid deposits, which are seen particularly in association with type 2 diabetes in humans and with diabetes in a few other mammalian species, especially monkeys and cats. Aggregated IAPP has cytotoxic properties and is believed to be of critical importance for the loss of beta-cells in type 2 diabetes and also in pancreatic islets transplanted into individuals with type 1 diabetes. This review deals both with physiological aspects of IAPP and ...
Researchers first injected transgenic mice expressing human IAPP with preformed fibrils of synthetic IAPP, proIAPP, or beta-amyloid. After 10 months on a high-fat diet, tissue was analyzed using an amyloid-specific dye. The number of islets with amyloid was significantly increased compared to controls by all three types of fibrils, and the amyloid consisted of IAPP in all groups. No amyloid deposits were found in the spleen, kidney, liver, heart, or lungs. The results demonstrate for the first time that fibril injections could seed amyloid formation in the pancreas and also that brain amyloid could cross-seed fibril formation in the pancreas.. In subsequent experiments the investigators analyzed human tissues from the pancreas and brain. Using antibody-based methods, they found that pancreas sections with islet amyloid from patients diagnosed with T2D showed no ...
Misfolding and aggregation of normally soluble proteins into amyloid fibrils and their deposition and accumulation underlies a variety of clinically significant diseases. Fibrillar aggregates with amyloid-like properties can also be generated in vitro from pure proteins and peptides, including those not known to be associated with amyloidosis. Whereas biophysical studies of amyloid-like fibrils formed in vitro have provided important insights into the molecular mechanisms of amyloid generation and the structural properties of the fibrils formed, amyloidogenic proteins are typically exposed to mild or more extreme denaturing conditions to induce rapid fibril formation in vitro. Whether the structure of the resulting assemblies is representative of their natural in vivo counterparts, thus, remains a ...
Amyloidosis is a protein conformational disorder in which amyloid fibrils accumulate in the extracellular space and induce organ dysfunction. Recently, two different amyloidogenic proteins, transthyretin (TTR) and apolipoprotein A-I (Apo A-I), were identified in amyloid deposits in knee joints in patients with knee osteoarthritis (OA). However, clinicopathological differences related to those two kinds of amyloid deposits in the knee joint remain to be clarified. Here, we investigated the clinicopathological features related to these knee amyloid deposits associated with knee OA and the biochemical characteristics of the amyloid deposits. We found that all of our patients with knee OA had amyloid deposits in the knee joints, especially in the meniscus, and those deposits were primarily derived from TTR and/or Apo A-I. Some ...
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. ...
BACKGROUND: The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimers disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon-prostate tissue remodelling in middle-aged and elderly men. METHODOLOGY/PRINCIPAL FINDINGS: By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced ...
Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a cross-beta x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common beta-sheet core structure, they display a substantial degree of morphological variation. One striking example is the remarkable ability of human apolipoprotein C-II amyloid fibrils to circularize and form closed rings. Here we explore in detail the structure of apoC-II amyloid fibrils using electron microscopy, atomic force microscopy, and x-ray diffraction studies. Our results suggest a model for apoC-II fibrils as ribbons approximately 2.1-nm thick and 13-nm wide with a helical repeat distance of 53 nm +/- 12 nm. We propose that the ribbons are highly flexible with a persistence length of 36 nm. We use these observed biophysical properties to model the apoC-II amyloid fibrils either ...
TY - JOUR. T1 - An insulin-degrading enzyme inhibitor decreases amylin degradation, increases amylin-induced cytotoxicity, and increases amyloid formation in insulinoma cell cultures. AU - Bennett, Robert G. AU - Hamel, Frederick G. AU - Duckworth, William C.. PY - 2003/9/1. Y1 - 2003/9/1. N2 - Amylin (islet amyloid polypeptide) is the chief component of the islet amyloid found in type 2 diabetes, and amylin fibril precursors may be cytotoxic to pancreatic β-cells. Little is known about the prevention of amylin aggregation. We investigated the role of insulin-degrading enzyme (IDE) in amylin degradation, amyloid deposition, and cytotoxicity in RIN-m5F insulinoma cells. Human 125I-labeled amylin degradation was inhibited by 46 and 65% with the addition of 100 nmol/l human amylin or insulin, respectively. 125I-labeled insulin degradation was inhibited with 100 nmol/l human amylin, rat amylin, and insulin (by ...
It has long been understood that amyloids can be lethal in systemic diseases. More recently, it has been accepted that local cerebral aggregation of the small peptide A beta is involved in the pathogenesis of Alzheimers disease. Protein aggregation, with the generation of small amyloid deposits in specific organs, also occurs outside the central nervous system and often is associated with increased cell death. In this review, we discuss two lesser known but common localized amyloid fibril-forming proteins: the polypeptide hormone islet amyloid polypeptide (IAPP) and the lactadherin-derived peptide medin. IAPP aggregates and induces the depletion of islet beta-cells in type 2 diabetes and in islets transplanted into type 1 diabetic subjects. Initial amyloid deposition occurs intracellularly and parts of this ...
Background: The L68Q variant of cystatin C is highly amyloidogenic forming aggregates in individuals with HCCAA. Results: Spermatozoa from mice expressing human L68Q cystatin C exhibit fertility defects and increased levels of amyloid. Conclusion: L68Q epididymal fluid containing cystatin C amyloid is harmful for sperm function. Significance: Amyloid in the reproductive tract may contribute to male factor infertility. Hereditary cystatin C amyloid angiopathy is an autosomal dominant disorder in which a variant form of cystatin C (L68Q) readily forms amyloid deposits in cerebral arteries in affected individuals resulting in early death. L68Q protein deposits in human cystatin C amyloid angiopathy patients have also been found in tissues outside of the brain including the testis, suggesting possible effects on fertility. Heterozygous transgenic mice (L68Q) that express the ...
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This study describes a technique which makes it possible to introduce the amyloid-like order to protein aggregates by using the scaffolding framework built from supramolecular, fibrillar Congo red structures arranged in an electric field. The electric field was used not only to obtain a uniform orientation of the charged dye fibrils, but also to make the fibrils long, compact and rigid due to the delocalization of pi electrons, which favors ring stacking and, as a consequence, results in an increased tendency to self-assemble. The protein molecules (immunoglobulin L chain lambda, ferritin) attached to this easily adsorbing dye framework assume its ordered structure. The complex precipitating as plate-like fragments shows birefringence in polarized light. The parallel organization of fibrils can be observed with an electron microscope. The dye framework may be removed via reduction with sodium dithionite, leaving the aggregated protein ...
The self-assembly of specific proteins to form insoluble amyloid fibrils is a characteristic feature of a number of age-related and debilitating diseases. Lipid-free human apolipoprotein C-II (apoC-II) forms characteristic amyloid fibrils and is one of several apolipoproteins that accumulate in amyloid deposits located within atherosclerotic plaques. X-ray diffraction analysis of aligned apoC-II fibrils indicated a simple cross-beta-structure composed of two parallel beta-sheets. Examination of apoC-II fibrils using transmission electron microscopy, scanning transmission electron microscopy, and atomic force microscopy indicated that the fibrils are flat ribbons composed of one apoC-II molecule per 4.7-A rise of the cross-beta-structure. Cross-linking results using single-cysteine substitution mutants are consistent with a parallel in-register structural model for apoC-II fibrils. ...
The amyloid diseases (amyloidoses) are classified according to the type of amyloid protein present as well as the underlying disease. Amyloid diseases have a number of common characteristics including each amyloid consisting of a unique type of amyloid protein. The amyloid diseases include, but are not limited to, the amyloid associated with Alzheimers disease, Downs syndrome, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, dementia pugilistica, inclusion body myositosis (Askanas et al,Ann. Neurol 43:521-560, 1993) and mild cognitive impairment (where the specific amyloid is referred to as beta-amyloid protein or Ap), the amyloid associated with chronic inflammation, various forms of malignancy and Familial Mediterranean Fever (where the ...
Serum amyloid P and CPHPC complex. Molecular model showing 5 molecules of the anti-amyloid drug CPHPC (spheres) bound to a serum amyloid P (SAP) molecule (shown here as both ribbons and spacefilled models, colourful). CPHPC is a small molecule able to strip amyloid P (AP) from deposits by reducing levels of circulating SAP. It can be used to help treat amyloidosis, a disease caused by a build-up of amyloid (insoluble fibrous protein aggregates) in body tissues that leads to organ failure. The symmetrical nature of CPHPC allows it to bind to two SAP subunits from different SAP molecules. This allows five molecules of CPHPC to bind two SAP pentamers together and it is this mechanism of action that potently removes SAP from amyloid deposits in the tissues. This behaviour may also provide a new approach for treating both systemic amyloidosis and diseases ...
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, ...
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 ...
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Protein aggregation is the cause of several human diseases such as diabetes mellitus type 2, Parkinson s disease, Alzheimer s disease, Huntington s disease, spongiform encephalopathies, congestive heart failure or dialysis-related amyloidosis. All of these disorders result from protein misfolding which leads to fibrillization and deposition of amyloid plaques in different parts of the body.Due to high molecular weight of the amyloid fibrils and intrinsic heterogeneity of the intermediate states, protein aggregation is a very challenging field of study for the structural biologist. However, nuclear magnetic resonance (NMR) provides a unique possibility to investigate aggregation at all stages, from the monomer to the fibrils.In this work, structural changes involved in prion ...
Wild-type transthyretin amyloid (WTTA), also known as senile systemic amyloidosis (SSA) and abbreviated as ATTR, is a disease that typically affects the heart and tendons of elderly people. It is caused by accumulation of a wild-type (that is to say a normal) protein called transthyretin. This is in contrast to a related condition called transthyretin-related hereditary amyloidosis where a genetically mutated transthyretin protein tends to deposit at a much earlier age than in WTTA, due to abnormal conformation and bioprocessing. It belongs to a group of diseases called amyloidosis, chronic progressive conditions linked to abnormal deposition of normal or abnormal proteins, because these proteins are misshapen and cannot be properly degraded and eliminated by the cell metabolism. Wild-type transthyretin amyloid accumulates mainly in the heart, where it ...
Background Hereditary transthyretin amyloid (ATTRm) amyloidosis is a systemic disease mainly affecting the peripheral nervous system and the heart. The disease is inherited in an autosomal dominant manner with a varying penetrance. It is caused by mutations in the transthyretin (TTR) gene. Today more than 100 disease causing mutations are known. The V30M mutation that is endemic in northern Sweden is the best studied and comprises the majority of the reported disease cases in the world. In ATTRm amyloidosis caused by the V30M mutation two distinct sub populations are seen, one with disease onset early in life and a mainly neuropathic disease and the other with late onset disease and both neuropathic disease and a progressive cardiomyopathy. These phenotypical findings have in Swedish patients been tied to differences in amyloid fibril composition. Generally, patients with early onset disease have amyloid fibrils containing ...
Transthyretin (TTR) is one of thirty non-homologous proteins whose misfolding, dissociation, aggregation, and deposition is linked to human amyloid diseases. Previous studies have identified that TTR amyloidogenesis can be inhibited through stabilization of the native tetramer state by small molecule binding to the thyroid hormone sites of TTR. We have evaluated a new series of β-aminoxypropionic acids (compounds 5-21), with a single aromatic moiety (aryl or fluorenyl) linked through a flexible oxime tether to a carboxylic acid. These compounds are structurally distinct from the native ligand thyroxine and typical halogenated biaryl NSAID-like inhibitors to avoid off-target hormonal or anti-inflammatory activity. Based on an in vitro fibril formation assay, five of these compounds showed significant inhibition of TTR amyloidogenesis, with two fluorenyl compounds displaying inhibitor efficacy ...
Results were recently published for the first trial of CPHPC as a therapy to clear out age-related deposits of the type of amyloid formed from misfolded transthyretin, normally responsible for transporting the thyroid hormone thyroxine in blood and cerebrospinal fluid. Amyloids are one of the distinguishing features of older tissues, and clearing them will be one of the necessary outcomes produced by any comprehensive suite of rejuvenation therapies developed in the near future.. The accumulation of transthyretin amyloid creates a condition known as senile systemic amyloidosis where it occurs to varying degrees for everyone in later life, and TTR amyloidosis when it arises in young people due to inherited mutations. Senile systemic amyloidosis is known to be responsible for a sizable fraction of deaths in supercentenarians, as the amyloid deposits clog the cardiovascular system to the point ...
Per Hammarstr�m, Frank Schneider, and Jeffery W. Kelly http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/2/or18 Abstract: Science 293, 2459-2462 (2001).. The transthyretin (TTR) amyloid diseases, representative of numerous misfolding disorders, are of considerable interest because there are mutations that cause or suppress disease. The Val30>Met30 (V30M) TTR mutation is the most prevalent cause of familial amyloid polyneuropathy in heterozygotes, whereas a Thr119>Met119 (T119M) mutation on the second TTR allele protects V30M carriers from disease. Here, we show that the incorporation of one or more T119M TTR subunits into a predominantly V30M tetramer strongly stabilized the mixed tetramer against dissociation. Dissociation is required for amyloid formation, so these findings provide a molecular explanation for intragenic trans-suppression of amyloidosis. The data also suggest a potential therapeutic strategy, provide insight ...
Dr. El-Agnaf is considered a pioneer in the field of Parkinsons disease and related disorders. In 1998, Dr El-Agnaf demonstrated for the first time that mutations in α-synuclein protein associated with familial cases of Parkinsons disease increased the tendency of the α-synuclein to aggregate and form amyloid-like fibrils compared to the wild-type protein. Several inventions have emerged from his research, including the unexpected discovery that neuronal cells constitutively release α-synuclein protein into the culture medium, and α-synuclein is normally present in human CSF and peripheral plasma. His discoveries have greatly impacted the scientific research community, provided further insight into the molecular pathogenesis of Parkinsons disease, and offered new opportunities for the development of novel diagnostic and therapeutic tools for Parkinsons disease. His research has also been translated into clinical studies to evaluate the ...
Dr. El-Agnaf is considered a pioneer in the field of Parkinsons disease and related disorders. In 1998, Dr El-Agnaf demonstrated for the first time that mutations in α-synuclein protein associated with familial cases of Parkinsons disease increased the tendency of the α-synuclein to aggregate and form amyloid-like fibrils compared to the wild-type protein. Several inventions have emerged from his research, including the unexpected discovery that neuronal cells constitutively release α-synuclein protein into the culture medium, and α-synuclein is normally present in human CSF and peripheral plasma. His discoveries have greatly impacted the scientific research community, provided further insight into the molecular pathogenesis of Parkinsons disease, and offered new opportunities for the development of novel diagnostic and therapeutic tools for Parkinsons disease. His research has also been translated into clinical studies to evaluate the ...
TY - JOUR. T1 - Amylin and diabetic cardiomyopathy - amylin-induced sarcolemmal Ca2+ leak is independent of diabetic remodeling of myocardium. AU - Liu, Miao. AU - Hoskins, Amanda. AU - Verma, Nirmal. AU - Bers, Donald M. AU - Despa, Sanda. AU - Despa, Florin. PY - 2017. Y1 - 2017. N2 - Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca2+ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the ...
Transthyretin (TTR) is a homotetrameric serum protein associated with amyloidoses such as familial amyloid polyneuropathy and senile systemic amyloidosis. The amyloid fibril formation of TTR can be inhibited through stabilization of the TTR tetramer by the binding of small molecules. In this study, we examined the inhibitory potency of caffeic acid phenethyl ester (CAPE) and its derivatives. Thioflavin T assay showed that CAPE suppressed the amyloid fibril formation of TTR. Comparative analysis of the inhibitory potencies revealed that phenethyl ferulate was the most potent among the CAPE derivatives. The binding of phenethyl ferulate and the selected compounds to TTR were confirmed by the 8-anilino-1-naphthalenesulfonic acid displacement and X-ray crystallography. It was also demonstrated that Bio 30, which is a CAPE-rich commercially available New Zealand propolis, inhibited ...
Amyloidosis, transthyretin-related (AMYL-TTR) [MIM:105210]: A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor. ...
TY - JOUR. T1 - Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy. AU - Taguchi, Kazuaki. AU - Jono, Hirofumi. AU - Kugimiya-Taguchi, Tomoe. AU - Nagao, Saori. AU - Su, Yu. AU - Yamasaki, Keishi. AU - Mizuguchi, Mineyuki. AU - Maruyama, Toru. AU - Ando, Yukio. AU - Otagiri, Masaki. PY - 2013/12/18. Y1 - 2013/12/18. N2 - Aims: Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo. Main methods: For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant ...
Define familial amyloidosis. familial amyloidosis synonyms, familial amyloidosis pronunciation, familial amyloidosis translation, English dictionary definition of familial amyloidosis. n. Any of a group of diseases or conditions characterized by the formation and deposition of amyloid in various organs and tissues of the body.
We identified amyloid derived from a mutant fibrinogen A alpha chain associated with one of the hereditary amyloidoses by kidney biopsy. The recognition of molecular and etiologic diversity among amyloidoses has revolutionized the management of systemic amyloidosis and necessitates precision in amyloid typing. Pitfalls and recommendations for the differential diagnosis of renal amyloid and current standards of amyloid typing are briefly discussed. Diagnosis of the amyloidosis type must be based on identification of the chemical composition of the amyloid protein in deposits and not on clinical suspicion, laboratory tests, or genetic testing. A clinical correlation is required to support but not make a diagnosis of amyloid type. If a hereditary form is detected by amyloid protein typing, then ...
The cause of the electrocardiographic abnormalities in amyloidosis is a matter of controversy despite attempts of clinicopathological correlation. Detailed correlative studies of the involvement of cardiac conduction system in amyloidosis are few and have produced conflicting results. Some authors favour the hypothesis that infiltration of the conducting system by amyloid deposits is the main reason for the disturbances of conduction [19]. In familial amyloidosis with polyneuropathy, amyloid infiltration of the sinus node and atrioventricular conduction system is now well documented, and this seems to account for the majority of the electrophysiological disturbances of these regions [20, 21, 22].The distribution and extent of heart infiltration by amyloid are not, however, uniform. On the other hand, other authors have concluded that direct infiltration by amyloid is of lesser importance ...
Familial amyloid polyneuropathy type I is an autosomal dominant disorder caused by mutations in the transthyretin (TTR) gene; however, carriers of the same mutation exhibit variability in penetrance and clinical expression. We analyzed alleles of candidate genes encoding non-fibrillar components of TTR amyloid deposits and a molecule metabolically interacting with TTR [retinol-binding protein (RBP)], for possible associations with age of disease onset and/or susceptibility in a Portuguese population sample with the TTR V30M mutation and unrelated controls. We show that the V30M carriers represent a distinct subset of the Portuguese population. Estimates of genetic distance indicated that the controls and the classical-onset group were furthest apart, whereas the late-onset group appeared to differ from both. Importantly, the data also indicate that genetic interactions among the multiple loci evaluated, rather than single-locus effects, are more likely to ...
Looking for online definition of amyloid nephrosis in the Medical Dictionary? amyloid nephrosis explanation free. What is amyloid nephrosis? Meaning of amyloid nephrosis medical term. What does amyloid nephrosis mean?
TY - JOUR. T1 - Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency. AU - Calingasan, Noel Y.. AU - Gandy, Samuel E.. AU - Baker, Harriet. AU - Sheu, Kwan Fu Rex. AU - Smith, Jonathan D.. AU - Lamb, Bruce T.. AU - Gearhart, John D.. AU - Buxbaum, Joseph D.. AU - Harper, Clive. AU - Selkoe, Dennis J.. AU - Price, Donald L.. AU - Sisodia, Sangram S.. AU - Gibson, Gary E.. PY - 1996/9/1. Y1 - 1996/9/1. N2 - Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in ...
Breathnach, S. "Amyloid and amyloidosis". J Am Acad Dermatol. vol. 18. 1988. pp. 1-16. (This 1988 review still offers an excellent overview of primary systemic amyloidosis. Although the prognosis and treatment information is outdated, the sections covering the pathogenesis, histopathology clinical/diagnostic features (including cutaneous findings with images) comprehensively summarizes the current information found in the literature for primary systemic amyloidosis. This manuscript also provides a decent overview of primary localized cutaneous amyloidosis but most of the text is dedicated to primary systemic amyloidosis.). Borowicz, J, Gillespie, M, Miller, R. "Cutaneous amyloidosis". Skinmed. vol. 2. 2011. pp. 96-100. (Within this brief overview of cutaneous amyloidosis, this manuscript provides a current summary of the treatment options for nodular cutaneous ...
A clinicopathologic study was made of 16 patients with amyloidosis and with clinical signs of intestinal pseudo-obstruction. amyloid deposits in the small intestine were proved in all cases by endoscopic or intra-operative biopsies, and immunohistochemical study identified the chemical types of amyloid protein: amyloid A protein (AA) in 13 cases, light chain protein (AL) in two, and beta 2-microglobulin (AH) in one. Clinically, an acute self limiting obstructive condition was evident in 13 cases with AA, and 12 of them returned to normal bowel function after receiving total parenteral nutrition. Two cases with AL and one with AH presented chronic, intermittent, obstructive symptoms, and medical treatment, including total parenteral nutrition, was ineffective with no recovery of intestinal propulsion. Pathological examination of the necropsy specimens in seven cases showed considerable ...
Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, we report the purification and electron cryo-microscopy analysis of amyloid fibrils from a mouse and a human patient with systemic AA amyloidosis. The obtained resolutions are 3.0 Å and 2.7 Å for the murine and human fibril, respectively. The two fibrils differ in fundamental properties, such as presence of right-hand or left-hand twisted cross-β sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar β-arch conformations within the N-terminal ~21 residues. Our data demonstrate the importance of the fibril protein N-terminus for the stability of the analyzed amyloid fibril morphologies and suggest ...
Immunoglobulin light chain amyloidosis (AL) is a plasma cell dyscrasia characterized by deposition of amyloid fibrils in various organs and tissues, derived from monoclonal light chains, leading to organ dysfunction.1-3 High-dose melphalan with autologous stem cell transplant (HDM/SCT) is an effective treatment with high complete hematologic response rates (CR) and is capable of producing durable remissions and prolonged overall survival.4-6 Only selected patients are eligible to receive HDM/SCT, and treatment-related mortality is in the range of 5-15%. More effective and widely applicable treatment modalities in AL amyloidosis are, therefore, needed.. Clinical trials of alternate treatment options have tested non-transplant melphalan-based strategies and novel therapeutics such as lenalidomide and bortezomib. Oral melphalan and dexamethasone (M-Dex) is a standard regimen for patients not eligible to receive HDM/SCT; reported complete response rates range ...
Production of soluble amyloid peptide precursor (APP) and amyloid peptide (A beta) was measured in CHO cells transfected by the wild-type APP 695 cDNA sequence or by the same sequence carrying missense mutations associated with familial Alzheimers disease in Sweden. Deletion of the C-terminal domain of the protein corresponding to residues 654 to 695 of APP 695 not only inhibited very significantly the internalization of APP at 37 degrees C, but also led to the secretion of an uncleaved APP in the culture medium of CHO cells. This deletion did not affect A beta production from the Swedish APP but was able to inhibit the production of the wild-type APP. These results demonstrate that, in CHO cells, the internalization of the wild-type APP is needed for A beta production, while the production of the amyloid peptide from Swedish APP is independent of the internalization process. ...
Familial Amyloid Polyneuropathy (FAP) is a rare, hereditary disease caused by mutations in the transthyretin (TTR) protein. TTR is made by the liver and secreted into the blood. TTR mutations cause it to misfold and deposit in multiple organs causing FAP.. IONIS-TTR Rx is an antisense drug that is designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein will result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression.. The purpose of this study is to determine if IONIS-TTR Rx can slow or stop the nerve damage caused by TTR deposits. This study will enroll late Stage 1 and early Stage 2 FAP patients. Patients will receive either IONIS-TTR Rx or placebo for 65 weeks. ...
Familial Amyloid Polyneuropathy (FAP) is a rare, hereditary disease caused by mutations in the transthyretin (TTR) protein. TTR is made by the liver and secreted into the blood. TTR mutations cause it to misfold and deposit in multiple organs causing FAP.. IONIS-TTR Rx is an antisense drug that is designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein will result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression.. The purpose of this study is to determine if IONIS-TTR Rx can slow or stop the nerve damage caused by TTR deposits. This study will enroll late Stage 1 and early Stage 2 FAP patients. Patients will receive either IONIS-TTR Rx or placebo for 65 weeks. ...
TY - JOUR. T1 - Persistent fever and destructive arthritis caused by dialysis-related amyloidosis. AU - Matsumoto, Kotaro. AU - Kikuchi, Jun. AU - Kaneko, Yuko. AU - Yasuoka, Hidekata. AU - Suzuki, Kazuko. AU - Tokuyama, Hirobumi. AU - Kameyama, Kaori. AU - Yamaoka, Kunihiro. AU - Takeuchi, Tsutomu. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Rationale: Dialysis-related amyloidosis (DRA) can present rheumatic manifestations in patients on long-term hemodialysis. Typical articular symptoms with DRA involve carpal-tunnel syndrome, effusion in large joints, spondyloarthropathy, or cystic bone lesions, which are usually with non-inflammatory processes. Patient concerns: A 64-year-old man on hemodialysis for ,30 years was admitted because of intermittent fever, polyarthritis, and elevated serum C-reactive protein (CRP) level, which was continuous for 2 years. Several antibiotics were ineffective for 3 months before his admission. On physical examination, joint swelling ...
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Background: Familial amyloid polyneuropathy related to transthyretin gene (TTR-FAP) is a life-threatening disease transmitted as an autosomal dominant trait. Val30Met mutation accounts for the majority of the patients with large endemic foci especia
TY - JOUR. T1 - Familial amyloid polyneuropathy (FAP), in an inborn habitat of Hiroshima Prefecture, Japan. AU - Nitta, K.. AU - Kito, S.. AU - Harada, T.. AU - Sakaki, Y.. AU - Sasaki, H.. PY - 1986/9/1. Y1 - 1986/9/1. UR - http://www.scopus.com/inward/record.url?scp=0022784075&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0022784075&partnerID=8YFLogxK. M3 - Article. C2 - 3791769. AN - SCOPUS:0022784075. VL - 26. SP - 903. EP - 906. JO - Clinical Neurology. JF - Clinical Neurology. SN - 0009-918X. IS - 9. ER - ...
TY - JOUR. T1 - Immunoglobulin light chain amyloidosis is diagnosed late in patients with preexisting plasma cell dyscrasias. AU - Kourelis, Taxiarchis. AU - Kumar, Shaji K. AU - Go, Ronald S.. AU - Kapoor, Prashant. AU - Kyle, Robert A.. AU - Buadi, Francis K.. AU - Gertz, Morie. AU - Lacy, Martha. AU - Hayman, Suzanne R.. AU - Leung, Nelson. AU - Dingli, David M. AU - Lust, John A.. AU - Lin, Yi. AU - Zeldenrust, Stephen R.. AU - Rajkumar, S Vincent. AU - Dispenzieri, Angela. PY - 2014/11/1. Y1 - 2014/11/1. N2 - AL amyloidosis (AL) is rare and frequently remains undiagnosed until organ function is compromised, even among patients with known pre-existing untreated plasma cell dyscrasias (PCD). We identified 168 patients with AL amyloidosis who had a prior untreated PCD. The earliest symptom or sign (s/s) was defined as the first symptom reported by the patient that could be attributed to organ dysfunction caused by AL. The interval from the time of ...
Author Summary The transmissible agent of prion disease consists of a prion protein in its abnormal conformation (PrPSc), which replicates itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrPSc. The current study reports that infectious prions and transmissible prion disease can be triggered in wild type animals by amyloid fibrils produced from recombinant prion prtotein, which are structurally different from PrPSc and lacks any detectable PrPSc particles. This work introduces a new hypothesis that transmissible prion diseases can be induced by prion protein structures different from that of authentic PrPSc and suggests that a new mechanism for triggering PrPSc formation different from the classical templating exists. The current work provides important new insight into the mechanisms underlying genesis and evolution ...
Title: Serum Amyloid Beta Peptides in Patients with Dementia and Age-Matched Non-Demented Controls as Detected by Surface-Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS). VOLUME: 3 ISSUE: 3. Author(s):Suzanne V. Frankfort, Jos P.C.M. van Campen, Linda R. Tulner and Jos H. Beijnen. Affiliation:Department of Pharmacy&Pharmacology, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.. Keywords:Serum Amyloid Beta Peptides, dementia, SELDI-TOF MS, Alzheimers Disease, CSF profile, diagnosis, DNA Isolation, Genotype Analysis. Abstract: Background: By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDITOF MS) an amyloid ß (Aß) profile was shown in cerebrospinal fluid (CSF) of patients with dementia. Objective: To investigate the Aβ-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of ...
TY - JOUR. T1 - Urine proteome scans uncover total urinary protease, prostaglandin D synthase, serum amyloid P, and superoxide dismutase as potential markers of lupus nephritis. AU - Wu, Tianfu. AU - Fu, Yuyang. AU - Brekken, Deirdre. AU - Yan, Mei. AU - Zhou, Xin J.. AU - Vanarsa, Kamala. AU - Deljavan, Nima. AU - Ahn, Chul. AU - Putterman, Chaim. AU - Mohan, Chandra. PY - 2010/2/15. Y1 - 2010/2/15. N2 - To identify potential biomarkers in immune-mediated nephritis, urine from mice subjected to an augmented passive model of antiglomerular basement membrane (GBM)-induced experimental nephritis was resolved using two-dimensional gels. The urinary proteome in these diseased mice was comprised of at least 71 different proteins. Using orthogonal assays, several of these molecules, including serum amyloid P (SAP), PG D synthase, superoxide dismutase, rennin, and total protease were validated to be elevated in the urine and kidneys of mice during anti-GBM disease, ...
The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study. Rodrigues MA, Samarasekera N, Lerpiniere C, et al. Lancet Neurol 2018; 17:232-240. Abstract BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated…
TY - JOUR. T1 - Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes. AU - Heyn, Sietske N.. AU - Vulliet, Philip R. PY - 2001/6/22. Y1 - 2001/6/22. N2 - Recent findings suggest that Presenilin 1 (PS1) mutations play a major role in the development of Alzheimers disease (AD) by increasing the production of the beta amyloid peptide (Aβ). The exact mechanism whereby mutations in PS1 lead to this effect is not clear. To examine the question of how PS1 might be involved in amyloid precursor protein (APP) processing, we constructed a chimera of human APP695 fused at the C-terminal to enhanced green fluorescent protein (EGFP). This construct was injected into Xenopus laevis oocytes in the presence of wild type PS1 or one of three PS1 mutations associated with AD. The cellular location of the APP695-EGFP construct was examined by fluorescent confocal ...
Ly et al: CAA Predisposes to rt-PA Related Hhemorrhage Cerebral b-Amyloid Detected by Pittsburgh Compound B Positron Emission Topography Predisposes to Recombinant Tissue Plasminogen Activator-Related Hemorrhage John V. Ly,1 Christopher C. Rowe,2 Victor L. Villemagne,2 Jorge A. Zavala,1 Henry Ma,1 Graeme OKeefe,2 Sylvia J. Gong,2 Rico Gunawan,1 Leonid Churilov,1 Tim Saunder,2 Uwe Ackerman,2 Henri Tochon-Danguy,2 and Geoffrey A. Donnan1,3 Cerebral amyloid angiopathy (CAA) may be an important predisposing factor for the hemorrhagic complications of recombinant tissue-type plasminogen activator (rt-PA) therapy. We studied patients treated within 3 hours of onset of ischemic stroke with rt-PA using positron emission tomography to compare Pittsburgh compound B (PiB) (a cerebral b-amyloid ligand) retention in those with and without parenchymal hemorrhage (PH) and normal controls. Neocortical PiB retention was higher among patients with PH compared with patients ...
As has been described in naturally occurring CAA (1, 5), vascular amyloid deposition in APP23 mice is most frequently found in arteries/arterioles and occurs most often in vessels outside the brain parenchyma proper (e.g., pia, fissures). The arterial predilection suggests that an anatomical difference between arteries and veins (e.g., presence of significant amounts of smooth muscle) could contribute to the development of CAA. Indeed, it has been hypothesized that Aβ is deposited by vascular smooth muscle cells and/or perivascular microglia, and APP expression and Aβ production by vascular cells have been well documented (22, 23). These reports and the observation that vessels apart from the neuropil are more often affected strongly implicate local production or circulating Aβ as an important source, although these hypotheses fail to explain the exclusive localization of CAA to cerebral vessels. In the present study, through examination of APP transgenic mice on an App-null background, we ...
Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 C or 100 C) and autoclaving (at 121 C or 135 C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 C, whereas autoclaving at 135 C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 C or autoclaved at 121 C, but not when autoclaved at 135 C. Transmissible ...
Lattice Corneal Dystrophy is associated with painful recurrent corneal erosions and amyloid corneal opacities induced by transforming growth factor β induced protein (TGFBIp) that impairs vision. The exact mechanism of amyloid fibril formation in Corneal Dystrophy is unknown but has been associated with destabilizing mutations in the fourth fasciclin 1 (Fas1-4) domain of TGFBIp. The green tea compound Epigallo-catechin gallate (EGCG) has been found to inhibit fibril formation of various amyloidogenic proteins in vitro. In this study we investigated the effect of EGCG as a potential treatment in Lattice Corneal Dystrophy (LCD) using Fas1-4 with the naturally occurring LCD-inducing A546T mutation. A few molar excess of EGCG were found to inhibit fibril formation in vitro by directing Fas1-4 A546T into stable EGCG-bound protein oligomers. Incubation with two molar equivalent EGCG led to a 4-fold reduction in ...
Meredith, J.E.; Thompson, L.A.; Toyn, J.H.; Marcin, L.; Barten, D.M.; Marcinkeviciene, J.; Kopcho, L.; Kim, Y.; Lin, A.; Guss, V.; Burton, C.; Iben, L.; Polson, C.; Cantone, J.; Ford, M.; Drexler, D.; Fiedler, T.; Lentz, K.A.; Grace, J.E.; Kolb, J.; Corsa, J.; Pierdomenico, M.; Jones, K.; Olson, R.E.; Macor, J.E.; Albright, C.F., 2008: P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors in mice
Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare, genetically heterogenous, and clinically variable autosomal dominant disease that severely reduces life expectancy. As treatment options grow, a proper diagnostic approach is mandatory especially in non-endemic regions with diverse genetic backgrounds. We examined 102 neuropathy patients at a German neuromuscular centre. Common causes of polyneuropathy were ruled out by medical history and extensive laboratory testing to define a cohort of patients with progressive polyneuropathy classified as idiopathic. Molecular genetic testing of the entire TTR gene was performed, and the detected amyloidogenic and non-amyloidogenic variants were associated with the observed clinical phenotypes and results of prior diagnostic testing. Two of 102 patients tested positive for amyloidogenic mutations (p.Ile127Val and p.Glu81Lys), while a variant of unknown significance, ...
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Background Icaritin (ICT) is a prenylflavonoid derivative from Epimedium brevicornum Maxim. ICT has been shown to have neuroprotective effects. We investigate how ICT affects secretion of amyloid precursor protein (APP). Methods We exposed APP-PS1-HEK293 cells to ICT to investigate its effect on beta-site amyloid cleaving enzyme (BACE)1. Cell viability was evaluated by MTT and lactate dehydrogenase (LDH) assays. The half-maximal inhibitory concentration (IC50) of ICT for BACE1 was measured using fluorescence resonance energy transfer. Effects of ICT on the mRNA expression of APP were assessed by quantitative polymerase chain reaction, and protein expression was measured by western blotting and immunofluorescence. Results Icaritin inhibited BACE1 activity and IC50 was 5.70 ± 1.09 μM. Compared with the control group, at ICT concentrations of 5 μM and 10 μM, the viability increased and LDH leakage decreased in APP-PS1-293 cells. Also, mRNA ...
We introduced criteria for the clinical diagnosis of dialysis-related amyloidosis (DRA) from the Amyloidosis Research Group study supported by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan. DRA exhibits various kinds of bone articular lesions, such as carpal tunnel syndrome, trigger finger, destructive spondyloarthropathy, spinal canal stenosis, and joint pains. These bone articular lesions, excluding destructive spondyloarthropathy, are observed in non-dialysis patients or dialysis patients without DRA. We carefully compared these lesions between DRA and non-DRA patients and summarized the differences between them. The incidence age, male to female ratio, and coincidence rate were distinct between these groups of patients. Biopsies from bone articular lesions are invasive and burdensome for dialysis patients; therefore, a precise clinical diagnosis is required for DRA. We discussed the validity and availability of our proposed criteria.
AA amyloidosis is a form of amyloidosis, a disease characterized by the abnormal deposition of fibers of insoluble protein in the extracellular space of various tissues and organs. In AA amyloidosis, the deposited protein is serum amyloid A protein (SAA), an acute-phase protein which is normally soluble and whose plasma concentration is highest during inflammation. AA amyloidosis is a complication of a number of inflammatory diseases and infections, although only a small portion of patients with these conditions will go on to develop AA amyloidosis. A natural history study of AA amyloidosis patients published in the New England Journal of Medicine reported a number of conditions associated with AA amyloidosis. The most common presentation of AA amyloidosis is renal in nature, including ...
age-related macular degeneration Genetics Home Reference provides information about age-related macular degeneration. hereditary cerebral amyloid angiopathy At least one mutation in the CST3 gene has been found to cause hereditary cerebral amyloid angiopathy, a condition characterized by stroke and a decline in intellectual function (dementia), which begins in mid-adulthood. The CST3 gene mutation that has been identified causes a form of hereditary cerebral amyloid angiopathy known as the Icelandic type. This mutation replaces the protein building block (amino acid) leucine with the amino acid glutamine at position 68 in the cystatin C protein (written as Leu68Gln or L68Q). This abnormal cystatin C protein is less stable and is more prone to cluster together (aggregate) than the normal protein. The aggregated protein forms clumps called amyloid deposits ...
Alzheimers disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimers disease with amyloid pathology. MRI guidance permitted selective ...
Amyloidosis is a disorder resulting from the abnormal deposition of a particular protein in various tissues of the body. The four most common forms of amyloidosis are: (1) light chain due to immunoglobulins; (2) secondary which is seen in chronic inflammatory states such as rheumatoid arthritis; (3) senile which is typically seen in those over the age of 80; and (4) heriditary. There are at least eight different proteins that have been recognized to cause the hereditary amyloidoses [2]. Of these, the amyloidgenicTTR (ATTR) protein is the most common, with the Val30Met (Portuguese type) being the most prevalent mutation causing ATTR (80% of cases) [2]. The most common manifestation of ATTR is a neuropathy, but clinical manifestations vary depending on the location of the mutation. The treatment of hereditary amyloidosis is OLT, which limits further synthesis of the mutated ...
0036] There are many other diseases in addition to Alzheimers that progress with simultaneous changes in both proteins such as, for example but without limitation, moderate cognitive disorders or deficits, hereditary cerebral hemorrhage with amyloidosis-Dutch type, cerebral amyloid angiopathy, dementia associated with Parkinsons disease, neurodegenerative disease due to diffuse Lewy bodies, corticobasal degeneration, sub-acute sclerosing panencephalitis, dementia with argyrophilic grain disease and familial Gerstmann-Straussler-Scheinker disease. Therefore, another preferred embodiment of this aspect of the invention refers to the use of a compound of chemical structure (I) for the preparation of a medicinal drug for the prevention and/or treatment of a pathology related to increase in β-amyloid and hyperphosphorylation of tau that is selected from the list comprising: Alzheimers disease, moderate cognitive disorders or deficits, hereditary ...
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Groundbreaking research from the University of Alberta has identified the structure of the infectious prion protein, the cause of "mad cow disease" or BSE, chronic wasting disease in deer and elk and Creutzfeldt-Jakob disease in humans, which has long remained a mystery.. The infectious prion protein is a misfolded protein, which makes it very difficult to purify and study. Since it clumps together, standard structural biology techniques cannot be used to study it. Since the protein was first purified in the 1980s researchers have made limited insights into the structure of the protein.. The collaborative study, published in PLOS Pathogens, used electron cryomicroscopy to collect high-resolution electron micrographs. This was the first time this technology has been used on amyloid fibrils of the infectious prion, which are a special form of clumped-together proteins that ...
In patients with cerebral venous thrombosis (CVT) the incidence of intracerebral hemorrhage (ICH) is estimated at about 37% and subarachnoid hemorrhage (SAH) at 1% of patients. A case with coincident occurrence of ICH, SAH and CVT in a patient with cerebral amyloid angiopathy (CAA) is reported....
Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment.. Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).. Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS ,1 year. Athletes with PCS ,1 year had higher RPQ scores and ...
TY - CHAP. T1 - Definition of organ involvement and treatment response in primary systemic amyloidosis (Al). T2 - A consensus opinion from the 10 th international symposium on amyloid and amyloidosis. AU - Gertz, Morie A.. AU - Comenzo, Ray. AU - Falk, Rodney H.. AU - Fermand, Jean Paul. AU - Hazenberg, Bouke P.. AU - Hawkins, Philip N.. AU - Merlini, Giampaolo. AU - Moreau, Philippe. AU - Ronco, Pierre. AU - Sanchorawala, Vaishali. AU - Sezer, Orhan. AU - Solomon, Alan. AU - Grateau, Giles. PY - 2004/1/1. Y1 - 2004/1/1. UR - http://www.scopus.com/inward/record.url?scp=17744382676&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=17744382676&partnerID=8YFLogxK. M3 - Chapter. SN - 0849335345. SN - 9780849335341. SP - 151. EP - 153. BT - Amyloid and Amyloidosis. PB - CRC Press. ER - ...
This is the first reported case of familial amyloid cardiomyopathy associated with TTR Ile122 in a white patient. The Ile122 mutation is present in 4% of African Americans and usually results in isolated cardiac amyloidosis from age 60 years onwards, presenting with cardiac failure and/or arrhythmia. Occasionally, there is associated carpal tunnel syndrome, and peripheral polyneuropathy has been reported.3 Amyloid deposits of wild-type TTR are found in 25% of hearts from people over 80 years old, examined after death.6 These deposits do not always cause clinical symptoms but the possibility of amyloidosis should be considered when treating elderly patients with heart failure, particularly in cases resistant to conventional treatment with diuretics and ACE inhibitors. The diagnosis of cardiac amyloidosis is suggested by an ECG showing small complexes and/or anterior Q waves in association with concentric left ventricular ...
Numerous transmembrane proteins, including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimers disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases. We have used an antisense oligonucleotide (ASO) approach to delineate the role of ADAM10 and tumour necrosis factor-α converting enzyme (TACE; ADAM17) in the ectodomain shedding of ACE and APP from human SH-SY5Y cells. Although the ADAM10 ASO and TACE ASO significantly reduced (, 81%) their respective mRNA levels and reduced the α-secretase shedding of APP by 60% and 30%, respectively, neither ASO reduced the shedding of ACE. The mercurial compound 4-aminophenylmercuric acetate (APMA) stimulated the shedding of ACE but not of APP. The APMA-stimulated secretase cleaved ACE at the same Arg-Ser bond in the juxtamembrane stalk as the constitutive secretase but was more sensitive to inhibition by a hydroxamate-based compound. ...
TY - JOUR. T1 - Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity. AU - Solesio, María E.. AU - Peixoto, Pablo M.. AU - Debure, Ludovic. AU - Madamba, Stephen M.. AU - de Leon, Mony J.. AU - Wisniewski, Thomas. AU - Pavlov, Evgeny. AU - Fossati, Silvia. PY - 2018/8/1. Y1 - 2018/8/1. N2 - Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimers disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was ...
In the present study, we found complete defects on MIBG myocardial scans in 8 of 12 patients and limited uptake in the remaining 4 in association with severe systemic autonomic dysfunction. The incidence and magnitude of myocardial accumulation of MIBG were independent of clinical findings, including neurologic disabilities, duration of the illness, extent of endomyocardial amyloid deposition, ECG QRS voltage and ventricular wall thickness. These findings strongly suggest that cardiac adrenergic denervation due to autonomic nervous degeneration ([28]) accounts for alterations in I-123 MIBG myocardial imaging in patients with familial amyloid polyneuropathy. The presence of small localized concentrations of MIBG in the LV anterior wall in some patients indicates that myocardial sympathetic innervation is not equally impaired in this disease.. As we have previously reported ([34]), Tc-99m PYP scintigraphy may have the potential to detect early myocardial ...
Localized cutaneous amyloidosis (LCA) refers to a condition characterized by the deposition of amyloid or amyloid-like proteins in the dermis. Localized cutaneous amyloidosis encompasses several conditions characterized by amyloid deposition, including macular amyloidosis and lichen amyloidosis.
This paper was funded by the Duke Clinical Research Institute. Dr. Khouri has received research support from and is a member of the Speakers Bureau of Alnylam Pharmaceuticals; and has received an honorarium from and a member of the Advisory Board of Pfizer. Dr. Felker has received research support from Amgen, Merck, Novartis, Otsuka America Pharmaceutical, and Roche Diagnostics; and has served as a consultant for Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medscape, LLC, Medtronic PLC, MyoKardia, Novartis, Trevena, Alynylam Pharmaceuticals, and Cardionomic. Dr. DeVore has received support from the American Heart Association, Amgen, the National Heart, Lung, and Blood Institute, and Novartis; and has been a consultant for Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ...
Title: Insulin-Degrading Enzyme: Structure-Function Relationship and its Possible Roles in Health and Disease. VOLUME: 15 ISSUE: 31. Author(s):A. Fernandez-Gamba, M. C. Leal, L. Morelli and E. M. Castano. Affiliation:Fundacion Instituto Leloir and Instituto de Investigaciones Bioquimicas de Buenos Aires, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Patricias Argentinas 435, Buenos Aires C1405BWE, Argentina.. Keywords:Insulin degrading enzyme, insulysin, metallopeptidases, amyloid β, peptides, Alzheimer, diabetes mellitus type 2, varicella zoster virus. Abstract: Insulin-degrading enzyme (IDE) or insulysin is a highly conserved Zn2+ -dependent endopeptidase with an "inverted" HxxEH motif. In vivo, IDE contributes to regulate the steady state levels of peripheral insulin and cerebral amyloid β peptide (Aβ) of Alzheimers disease. In vitro, substrates of IDE include a broad spectrum of peptides with relevant physiological functions such as atrial ...
This new book presents a summary of Alzheimers disease-related ischemic protein changes and gene expression as risk factors for the late-onset of sporadic Alzheimers disease, and their role in Alzheimers disease ischemic etiology. Ischemic brain changes were noted in the staining of different parts of an amyloid protein precursor, presenilin 1 and 2, tau protein, alfa-synuclein, and apolipoproteins A1, E and J.. Current advances in understanding the ischemic etiology of Alzheimers disease has revealed dysregulation of Alzheimers disease-associated genes including presenilin 1 and 2, β-secretase, amyloid protein precursor, apoptosis, autophagy, mitophagy, and tau protein. This book presents the relationship between these genes, dysregulated by cerebral ischemia, and the cellular and tissue neuropathology characteristic of Alzheimers disease. This book draws attention to the ...
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Dementia-Linked Presenilin Mutation Causes Abnormal Splicing. Hirotaka Watanabe, Dan Xia, Takahisa Kanekiyo, Raymond J. Kelleher III, and Jie Shen. (see pages 5085-5096). Presenilin is part of the γ-secretase complex that cleaves amyloid precursor protein (APP) to form β-amyloid (Aβ). Mutations in presenilin cause familial Alzheimers disease (AD) and frontotemporal dementia (FTD), but how such mutations affect γ-secretase function is unclear. Accumulation of Aβ suggests that γ-secretase is overactive in AD, but some presenilin mutations produce FTD without amyloid plaques, suggesting γ-secretase function is diminished. Furthermore, γ-secretase has targets besides APP, notably the signaling molecule Notch, and preventing cleavage of these products-either by reducing γ-secretase activity or by increasing its APP load-might contribute to cognitive impairment in AD and FTD. To address this question, Watanabe et al. created knock-in mice ...
Mammalian serum amyloid A (SAA) is a major acute phase protein that shows a massive increase in plasma concentration during inflammation. In the present study, we demonstrate that the expression of mouse SAA1 in serum was increased when infected with Candida albicans, a major human fungal pathogen, in a systemic infection model. We then set out to investigate the antifungal activity of SAA proteins against C. albicans. Recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) were expressed and purified in Escherichia coli. Both rhSAA1 and rmSAA1 exhibited a potent antifungal activity against C. albicans. We further demonstrate that rhSAA1 binds to the cell surface of C. albicans, disrupts cell membrane integrity, and induces rapid fungal cell death in C. albicans. Our finding expands the known functions of SAA1 and provides new insight into host-Candida interactions during fungal infection. ...
0034] Memapsin 2 (BACE1, β-secretase) is a membrane anchored aspartic protease. Although this enzyme is ubiquitously present in many mammalian organs, its functions in the brain are best studied. One of the most important physiological functions of memapsin 2 is the cleavage of a brain membrane protein β-amyloid precursor protein (APP). The hydrolytic product of APP C-terminal fragment is cleaved again by an intramembrane protease γ-secretase to generate a 40- or 42-residue β-amyloid peptide (Ar). Aβ has been shown to feedback down regulate the synaptic activity in neurons (Kamenetz et al., 2003; Lauren et al., 2009). Also, memapsin 2 produced APP N-terminal fragment is involved in the trimming of neurons and axons in the brain (Nikolaev et al., 2009). However, since excess levels of brain Aβ are intimately related to the pathogenesis of Alzheimers disease (Selkoe, 1999), there has been intensive effort to develop inhibitor drugs against ...
Amyloidosis is the most serious complication of FMF, leading to ESRD. According to older publications amyloidosis occurred in 60% of Turkish patients, in 27% of the non-Ashkenazi Jews, and in only 1-2% of Armenians living in the United States.11 12 The frequent occurrence of amyloidosis and its dramatic variation among different ethnic groups raises a question as to the inherent relation with FMF and whether it is transmitted by the gene for FMF or as a separate genetic trait. The fact that some subjects develop amyloidosis without febrile episodes (phenotype II) may suggest that the predilection for amyloid is a part of the underlying genetic background of FMF. Thus the search for a specific amyloid associated mutation may be a conceivable approach in order to test this hypothesis.. Colchicine has been shown to be effective in controlling attacks of FMF as well as preventing the development of ...
Alzheimers disease brain tissue. Light micrograph of entorhinal cortex brain tissue affected by Alzheimers disease. Two characteristic features are seen here: neurofibrillary tangles (brown) and neuritic plaques (grey). Neurofibrillary tangles are formed of abnormal filaments of tau protein, an internal structural component of healthy nerve cells. The pathogenic abnormal form has no struct- ural role, and damages the cells. The neuritic plaques are formed mainly of aggregations of the protein amyloid. Alzheimers disease causes progr- essive impairment of mental function, leading to memory loss, dementia and death. Stained with anti-tau serum. Magnification: x50 at 35mm size. - Stock Image M108/0423

Global analysis of protein structural changes in complex proteomes | Nature BiotechnologyGlobal analysis of protein structural changes in complex proteomes | Nature Biotechnology

We detect structural changes in aggregation-prone proteins and show the functional relevance of one of these proteins to the ... Changes in protein conformation can affect protein function, but methods to probe these structural changes on a global scale in ... To enable large-scale analyses of protein conformational changes directly in their biological matrices, we present a method ... Using our method, we assessed the structural features of more than 1,000 yeast proteins simultaneously and detected altered ...
more infohttps://www.nature.com/articles/nbt.2999?error=cookies_not_supported&code=f175fec2-c849-4c3b-a0c7-9ca5db11899e

The hairpin conformation of the amyloid β peptide is an important structural motif along the aggregation pathway | SpringerLinkThe hairpin conformation of the amyloid β peptide is an important structural motif along the aggregation pathway | SpringerLink

The amyloid β (Aβ) peptides are 39-42 residue-long peptides found in the senile plaques in the brains of Alzheimers disease ( ... Alzheimers disease Amyloid β peptide Hairpin Protein aggregation Neurotoxicity Responsible Editors: Lucia Banci and Claudio ... The hairpin conformation of the amyloid β peptide is an important structural motif along the aggregation pathway. ... Lazo ND, Grant MA, Condron MC, Rigby AC, Teplow DB (2005) Protein Sci 14:1581-1596PubMedCentralPubMedGoogle Scholar ...
more infohttps://link.springer.com/article/10.1007%2Fs00775-014-1131-8

Biochemistry and Structural BiologyBiochemistry and Structural Biology

Mechanism of amyloid protein aggregation and the role of inhibitors Linse, Sara LU (2019) In Pure and Applied Chemistry 91(2). ... Lipid-protein interactions in amyloid formation Sparr, Emma LU and Linse, Sara LU (2019) In Biochimica et Biophysica Acta - ... On the molecular mechanisms of the amyloid β-peptide aggregation Sanagavarapu, Kalyani LU (2019) Mark ... Secondary nucleation in amyloid formation Törnquist, Mattias LU ; Michaels, Thomas C.T.; Sanagavarapu, Kalyani LU ; Yang, ...
more infohttps://lup.lub.lu.se/search/search/organization/v1000650?start=&sort=year.desc&limit=50

Protein Amyloid Aggregation | Springer for Research & DevelopmentProtein Amyloid Aggregation | Springer for Research & Development

... focuses on methods for the characterization of aggregation processes that lead to the formation of amyloid fibrils and amyloid ... Computational Methods for Structural and Functional Studies of Alzheimers Amyloid Ion Channels ... Authoritative and practical, Protein Amyloid Aggregation: Methods and Protocols serves as an ideal guide for biochemists and ... Aggregation processes Amyloid fibrils Amyloid formation pathway Amyloidoses Human disease Pharmacology Therapeutic development ...
more infohttps://rd.springer.com/book/10.1007/978-1-4939-2978-8

Now You See Them, Now You Dont: The Amyloid Channel Hypothesis | ALZFORUMNow You See Them, Now You Don't: The Amyloid Channel Hypothesis | ALZFORUM

Structural changes of the prion protein in lipid membranes leading to aggregation and fibrillization. Biochemistry. 2003 Mar 25 ... β2M is found in amyloid deposits as full-length native protein. In contrast to other amyloid protein "misfolding" diseases, the ... Structural changes of the prion protein in lipid membranes leading to aggregation and fibrillization. Biochemistry 42(11):3295- ... Lysozyme also forms toxic amyloid deposits in humans. Mutations or partial protein unfolding of lysozyme leads to aggregation, ...
more infohttps://www.alzforum.org/webinars/now-you-see-them-now-you-dont-amyloid-channel-hypothesis

Famillial Mediterranean Fever • Başlık görüntüleniyor - AmyloidFamillial Mediterranean Fever • Başlık görüntüleniyor - Amyloid

Amyloids are insoluble fibrous protein aggregations sharing specific structural traits. Contents[hide] 1 Definition controversy ... Xu S. Aggregation drives misfolding in protein amyloid fiber formation. Amyloid 2007 Jun;14(2):119-31. PMID 17577685 ... 2 Diseases featuring amyloids 3 Non-disease amyloids 4 Amyloid biophysics 5 Amyloid pathology 6 Histological staining 7 See ... edit] Non-disease amyloids (mostly using the biophysical definition) Native amyloids in organisms Curli E. coli Protein (curlin ...
more infohttp://aileviakdenizatesi.com/viewtopic.php?f=32&t=552&p=2042

Famillial Mediterranean Fever • Başlık görüntüleniyor - AmyloidFamillial Mediterranean Fever • Başlık görüntüleniyor - Amyloid

Amyloids are insoluble fibrous protein aggregations sharing specific structural traits. Contents[hide] 1 Definition controversy ... Xu S. Aggregation drives misfolding in protein amyloid fiber formation. Amyloid 2007 Jun;14(2):119-31. PMID 17577685 ... 2 Diseases featuring amyloids 3 Non-disease amyloids 4 Amyloid biophysics 5 Amyloid pathology 6 Histological staining 7 See ... edit] Non-disease amyloids (mostly using the biophysical definition) Native amyloids in organisms Curli E. coli Protein (curlin ...
more infohttp://aileviakdenizatesi.com/viewtopic.php?f=32&t=552

Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which...Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which...

2014) Abeta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies. ... 2010) Amyloid beta-protein dimers rapidly form stable synaptotoxic protofibrils. J Neurosci 30:14411-14419, doi:10.1523/ ... 2011) Isolation of low-n amyloid beta-protein oligomers from cultured cells, CSF, and brain. Methods Mol Biol 670:33-44, doi: ... 2005) Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 11:556- ...
more infohttp://www.jneurosci.org/content/37/1/152?ijkey=eb617e9a39ca4dacb1ac6139ebaa33f8de710ce0&keytype2=tf_ipsecsha

Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which...Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which...

2014) Abeta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies. ... 2010) Amyloid beta-protein dimers rapidly form stable synaptotoxic protofibrils. J Neurosci 30:14411-14419, doi:10.1523/ ... 2011) Isolation of low-n amyloid beta-protein oligomers from cultured cells, CSF, and brain. Methods Mol Biol 670:33-44, doi: ... 2005) Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 11:556- ...
more infohttp://www.jneurosci.org/content/37/1/152

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimers disease |...Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease |...

... contribution of biophysical and structural studies of protein self-assembly to the design of therapeutic strategies for amyloid ... Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms. Sofia Giorgetti, Claudio Greco, Paolo Tortora, ... Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade ... dDepartment of Biochemistry & Structural Biology, Center for Molecular Protein Science, Lund University, 221 00 Lund, Sweden ...
more infohttps://www.pnas.org/content/114/2/E200/tab-article-info

Brain tissue with Alzheimers disease - Stock Image M108/0423 - Science Photo LibraryBrain tissue with Alzheimer's disease - Stock Image M108/0423 - Science Photo Library

The neuritic plaques are formed mainly of aggregations of the protein amyloid. Alzheimers disease causes progr- essive ... an internal structural component of healthy nerve cells. The pathogenic abnormal form has no struct- ural role, and damages the ... Neurofibrillary tangles are formed of abnormal filaments of tau protein, ... The neuritic plaques are formed mainly of aggregations of the protein amyloid. Alzheimers disease causes progr- essive ...
more infohttp://www.sciencephoto.com/media/250096/view

Inert and seed-competent tau monomers suggest structural origins of aggregation | eLifeInert and seed-competent tau monomers suggest structural origins of aggregation | eLife

Tau protein exists as two conformational ensembles, one inert, and another that has intrinsic properties of self-association, ... Amyloids are ordered protein assemblies, typically rich in beta sheet, that underlie multiple disorders such as Alzheimers ... Aggregation of Mi in vitro is relatively slow, requires high protein concentration (micromolar), and polyanions such as heparin ... Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta- ...
more infohttps://elifesciences.org/articles/36584

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation, Nature Structural & Molecular...Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation, Nature Structural & Molecular...

Nature Structural & Molecular Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of ... "Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation, ... Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity ... Structural transformation of the amyloidogenic core region of TDP-43 protein initiates its aggregation and cytoplasmic ...
more infohttps://www.deepdyve.com/lp/springer_journal/atomic-structures-of-tdp-43-lcd-segments-and-insights-into-reversible-0WRrfIzz4L

Conformational characterization of oligomeric intermediates and aggregates in β-lactoglobulin heat aggregation - Carrotta -...Conformational characterization of oligomeric intermediates and aggregates in β-lactoglobulin heat aggregation - Carrotta -...

... usually a signature of the amyloid superstructures found in many protein aggregates. This result suggests that the structural ... Protein aggregation: Folding aggregates, inclusion bodies and amyloid. Folding & Design 3: R9-R23. *CrossRef , ... Protein aggregation has important technical implications in biotechnology as well as in food science. Deposition of protein ... Amyloid β-protein fibrillogenesis. Detection of a protofibrillar intermediate. J. Biol. Chem. 272: 22364-22372. *CrossRef , ...
more infohttp://onlinelibrary.wiley.com/doi/10.1110/ps.42501/full

Tuning Protein Assembly Pathways through Superfast Amyloid-Like Aggregation - Biomaterials Science (RSC Publishing)Tuning Protein Assembly Pathways through Superfast Amyloid-Like Aggregation - Biomaterials Science (RSC Publishing)

However, amyloid aggregation of proteins in vitro generally requires a long incubation time under extremely harsh conditions, ... Amyloid formation of proteins is not only relevant for neurodegenerative diseases, but has recently emerged as a groundbreaking ... and the understanding on structural motif to determine amyloid assembly is extremely lacking. Herein we reveal that the ... Tuning Protein Assembly Pathways through Superfast Amyloid-Like Aggregation C. Li, L. Xu, Y. Zuo and P. Yang, Biomater. Sci., ...
more infohttp://pubs.rsc.org/en/content/articlelanding/2018/bm/c8bm00066b

Frontiers | Biophysical Insights into How Surfaces, Including Lipid Membranes, Modulate Protein Aggregation Related to...Frontiers | Biophysical Insights into How Surfaces, Including Lipid Membranes, Modulate Protein Aggregation Related to...

These diseases are commonly classified as protein misfolding or amyloid diseases. The interaction of these proteins with liquid ... Here, we review the influence of surfaces in driving and stabilizing protein aggregation with a specific emphasis on lipid ... A detailed understanding of the influence of (sub)cellular surfaces in driving protein aggregation and/or stabilizing specific ... A detailed understanding of the influence of (sub)cellular surfaces in driving protein aggregation and/or stabilizing specific ...
more infohttps://www.frontiersin.org/articles/10.3389/fneur.2013.00017/full

Computational Methods for Structural and Functional Studies of Alzheimers Amyloid Ion Channels | SpringerLinkComputational Methods for Structural and Functional Studies of Alzheimer's Amyloid Ion Channels | SpringerLink

Aggregation can be studied by a range of methods, experimental and computational. Aggregates form in solution, across solid ... In: Eliezer D. (eds) Protein Amyloid Aggregation. Methods in Molecular Biology, vol 1345. Humana Press, New York, NY. * DOI ... Glabe CG (2008) Structural classification of toxic amyloid oligomers. J Biol Chem 283:29639-29643PubMedCentralCrossRefPubMed ... β2-microglobulin amyloid fragment organization and morphology and its comparison to Aβ suggests that amyloid aggregation ...
more infohttps://link.springer.com/protocol/10.1007%2F978-1-4939-2978-8_16

The shape-shifting protein behind Alzheimers disease
 - Washington University in St. Louis EngineeringThe shape-shifting protein behind Alzheimer's disease - Washington University in St. Louis Engineering

Researchers have known that the peptide amyloid beta plays a role in causing Alzheimers disease, but they are still working to ... Somewhere on this aggregation pathway, this type of structural element is formed for the amyloid beta to get into the cell, ... Jin A, Kedia N, Illes-Toth E, Haralampiev I, Prisner S, Herrmann A, Wanker E, Bieschke J. Amyloid-b1-42 aggregation initiates ... and his collaborators found that the amyloid beta protein structure that was able penetrate the cell had a specific type of ...
more infohttps://engineering.wustl.edu/news/Pages/The-shape-shifting-protein-behind-Alzheimers-disease.aspx

Protein aggregation, structural disorder and RNA-binding ability: a new approach for physico-chemical and gene ontology...Protein aggregation, structural disorder and RNA-binding ability: a new approach for physico-chemical and gene ontology...

... such as structural disorder and aggregation, in S. cerevisiae, C. elegans, M. musculus and H. sapiens. Our results are in ... We illustrate the powerfulness of our approach by investigating the links between RNA-binding ability and other protein ... Here we introduce an innovative approach to discriminate multiple protein datasets (multiCM) and to measure enrichments in gene ... which is extremely useful for the discovery and characterization of new trends in protein datasets. The multiCM and cleverGO ...
more infohttps://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-015-2280-z

Recent Structural and Computational Insights into Conformational Diseases | BenthamScienceRecent Structural and Computational Insights into Conformational Diseases | BenthamScience

Keywords:Conformational diseases, amyloid fibrils, protein aggregation, protein folding, protein structure, Alzheimers disease ... Keywords: Conformational diseases, amyloid fibrils, protein aggregation, protein folding, protein structure, Alzheimers ... Protein Chemistry of Amyloid Fibrils and Chaperones: Implications for Amyloid Formation and Disease. Current Chemical Biology ... much effort has gone into elucidating the structural basis of protein aggregation. A number of recent experimental and ...
more infohttp://www.eurekaselect.com/67084/article

Items where Author is Juhász, Gábor - Repository of the Academys LibraryItems where Author is "Juhász, Gábor" - Repository of the Academy's Library

Structural basis and thermodynamics of protein aggregation and amyloid formation; in vivo effect of aggregates of different ... Beta-amyloid aggregation and interaction with proteins; novel neuroprotective compounds for prevention of Alzheimers disease. ... Varga, Edina and Juhász, Gábor and Bozsó, Zsolt and Penke, Botond and Fülöp, Lívia and Szegedi, Viktor (2015) Amyloid-β1-42 ... Hegedűs, Krisztina and Nagy, Péter and Gáspári, Zoltán and Juhász, Gábor (2014) The putative HORMA domain protein Atg101 ...
more infohttp://real.mtak.hu/view/creators/Juh=E1sz=3AG=E1bor=3A=3A.html

Items where Subject is Q Science / természettudomány | QH Natural history / természetrajz | QH301 Biology / biológia | QH3020...Items where Subject is "Q Science / természettudomány | QH Natural history / természetrajz | QH301 Biology / biológia | QH3020...

Structural basis and thermodynamics of protein aggregation and amyloid formation; in vivo effect of aggregates of different ... Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of Fibrillation by PEG. PROTEIN AND PEPTIDE LETTERS, 22 ... Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and ... Structural and nanomechanical comparison of epitaxially and solution-grown amyloid β25-35 fibrils. BIOCHIMICA ET BIOPHYSICA ...
more infohttp://real.mtak.hu/view/subjects/QH3020.html

The Next Frontier | The New York Academy of SciencesThe Next Frontier | The New York Academy of Sciences

The addition or removal of a phosphate group can have remarkable effects on a protein. Can this regulatory step be exploited to ... amyloid precursor protein (APP), which may be dysregulated in AD; and the Huntingtons disease protein huntingtin.. Use the ... A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 443: 774-779.. Paleologou KE, ... His research interests include the structural basis of amyloid-associated toxicity in neurodegenerative disease, developing ...
more infohttps://www.nyas.org/ebriefings/the-next-frontier/

Novel mass spectrometry approaches for protein structural dynamics (funded PhD studentship) at University of Leeds on FindAPhD...Novel mass spectrometry approaches for protein structural dynamics (funded PhD studentship) at University of Leeds on FindAPhD...

Novel mass spectrometry approaches for protein structural dynamics (funded PhD studentship) at University of Leeds, listed on ... in amyloid aggregation. While most "traditional" techniques will highlight either the most dominant (stable) form, or an ... Novel mass spectrometry approaches for protein structural dynamics (funded PhD studentship) University of Leeds. , Faculty of ... Novel mass spectrometry approaches for protein structural dynamics (funded PhD studentship). University of Leeds ...
more infohttps://www.findaphd.com/phds/project/novel-mass-spectrometry-approaches-for-protein-structural-dynamics-funded-phd-studentship/?p86283

Publications - Institute for Bioengineering of Catalonia (IBEC)Publications - Institute for Bioengineering of Catalonia (IBEC)

... much effort has gone into elucidating the structural basis of protein aggregation. A number of recent experimental and ... amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β ... Protein aggregation correlates with the development of several deleterious human disorders such as Alzheimers disease, ... Residue D48 of Hha protein is essential for the interaction with H-NS, thus the D48N substitution in Hha protein abrogates H-NS ...
more infohttps://www.ibecbarcelona.eu/for-researchers/publications/2015/
  • Protein aggregation correlates with the development of several deleterious human disorders such as Alzheimers disease, Parkinsons disease, prion-associated transmissible spongiform encephalopathies and type II diabetes. (eurekaselect.com)
  • Atomistic molecular dynamics (MD) simulations are capable of providing insight into structural details of amyloid ion channels in the membrane at a resolution not achievable experimentally. (springer.com)
  • 2000 ). Blg is a globular protein with a mass of 18.3 kD, and is the most abundant protein in bovine whey. (wiley.com)
  • Changes in protein conformation can affect protein function, but methods to probe these structural changes on a global scale in cells have been lacking. (nature.com)
  • Pelton, J.T. & McLean, L.R. Spectroscopic methods for analysis of protein secondary structure. (nature.com)
  • Authoritative and practical, Protein Amyloid Aggregation: Methods and Protocols serves as an ideal guide for biochemists and biophysicists with an interest in elucidating the mechanisms of protein amyloid formation, as well as chemists, pharmacologists, and clinicians with an interest in leveraging an understanding of such mechanisms for the purpose of therapeutic development. (springer.com)
  • Aggregation can be studied by a range of methods, experimental and computational. (springer.com)
  • We demonstrate the usefulness of our methods by investigating the RNA-binding abilities of S. cerevisiae chaperones and their substrates, the physico-chemical determinants of protein insolubility in S. cerevisiae , M. musculus and H. sapiens , and the relationship between aggregation and longevity in C. elegans . (biomedcentral.com)
  • High-resolution structural methods such as x-ray crystallography, NMR and now increasingly also EM (where we have excellent equipment in the Astbury Centre at Leeds) are making important contributions to our understanding of biomolecular structure and function. (findaphd.com)
  • Dr Paci is leading the theoretical biophysics group at Astbury Centre, currently focusing on HDX data analysis and structural bioinformatics methods. (findaphd.com)
  • The remainder of this article will be inclusive with due deference to the controversy by indicating where amyloid species are observed only in the biophysical context. (aileviakdenizatesi.com)
  • The conversion of a protein from a monomer to a large, ordered multimer could occur by several mechanisms, but the first step probably involves the formation of a seed. (elifesciences.org)
  • On the other hand, several computational approaches have identified regions prone to aggregation in disease-linked polypeptides, predicted the differential aggregation propensities of their genetic variants and simulated the early, crucial steps in protein self-assembly. (eurekaselect.com)
  • In combination with computational approaches (molecular modelling), we can build structural models of complex and dynamic systems. (findaphd.com)
  • Professor Sobott's internationally recognized team has developed and applied structural MS approaches for more than 20 years. (findaphd.com)
  • The project supervisors are all part of the Astbury Centre for Structural Molecular Biology at Leeds University, which has some of the best structural biology equipment (e.g. cryo-EM and NMR) and computational resources anywhere. (findaphd.com)
  • They collaborate on method development in structural proteomics and use of such data for computational modelling of structural dynamics. (findaphd.com)
  • The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting cross-beta structure. (aileviakdenizatesi.com)
  • In an intuitive way, multiCM and cleverGO provide accurate classifications of physico-chemical features and annotations of biological processes, molecular functions and cellular components, which is extremely useful for the discovery and characterization of new trends in protein datasets. (biomedcentral.com)
  • The purpose of our analysis is twofold: to provide examples that can be used as a reference in other studies and to shed light on the link between nucleic-acid binding abilities and protein features, such as structural disorder and aggregation, that are increasingly recognized as key factors for cellular function and homeostasis [ 7 - 9 ]. (biomedcentral.com)
  • The preferential nitrosylation in the Cys 90, Cys 152 and Cys 220 has been observed which alters the catalytic activity and structural stability. (pubmedcentralcanada.ca)
  • Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a deubiquitinating enzyme which is largely expressed in neuron, comprising almost 1-5% of total brain protein and its absence in mice due to intragenic deletions produces neurodegenerative phenotypes 12 , 13 . (pubmedcentralcanada.ca)
  • Ilari, A. & Savino, C. Protein structure determination by x-ray crystallography. (nature.com)
  • To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. (deepdyve.com)
  • Amyloid polymerization is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. (aileviakdenizatesi.com)
  • Monsonego A, Zota V, Karni A, Krieger JI, Bar-Or A, Bitan G, Budson AE, Sperling R, Selkoe DJ, Weiner HL (2003) Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. (springer.com)
  • Amyloid beta can interfere with the mitochondria, or the cell's energy powerhouse. (wustl.edu)
  • With this knowledge, Bieschke and his collaborators can investigate what happens next to amyloid beta once inside the cell and how it interacts with the mitochondria. (wustl.edu)
  • Although tau monomer has been considered to be natively unstructured, our findings belie this assumption and suggest that initiation of pathological aggregation could begin with conversion of tau monomer from an inert to a seed-competent form. (elifesciences.org)
  • The present study is a part of our ongoing effort to detect protein expression alterations in human frontal cortex as Lewy body deposition spreads from the brainstem to the limbic system and eventually to the isocortex with progression of PD ( 2 , 16 , 17 ). (mcponline.org)
  • citation needed] In melanocytic cells, SNCA protein expression may be regulated by MITF. (wikipedia.org)