Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
A 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.
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.
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.
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
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.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
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.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
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)
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
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).
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.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
Diseases in which there is a familial pattern of AMYLOIDOSIS.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
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.
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)
Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)
The 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.
The rate dynamics in chemical or physical systems.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
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.
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.
An abnormal protein with unusual thermosolubility characteristics that is found in the urine of patients with MULTIPLE MYELOMA.
An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC
Thiazoles are heterocyclic organic compounds containing a sulfur atom and a nitrogen atom, which are bound by two carbon atoms to form a five-membered ring, and are widely found in various natural and synthetic substances, including some pharmaceuticals and vitamins.
The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.
The thermodynamic interaction between a substance and WATER.
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.
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
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
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.
A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.
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.
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.
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.
Conformational transitions of the shape of a protein to various unfolded states.
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.
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.
A 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)
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

Evolution of Nova-dependent splicing regulation in the brain. (1/71)

A large number of alternative exons are spliced with tissue-specific patterns, but little is known about how such patterns have evolved. Here, we study the conservation of the neuron-specific splicing factors Nova1 and Nova2 and of the alternatively spliced exons they regulate in mouse brain. Whereas Nova RNA binding domains are 94% identical across vertebrate species, Nova-dependent splicing silencer and enhancer elements (YCAY clusters) show much greater divergence, as less than 50% of mouse YCAY clusters are conserved at orthologous positions in the zebrafish genome. To study the relation between the evolution of tissue-specific splicing and YCAY clusters, we compared the brain-specific splicing of Nova-regulated exons in zebrafish, chicken, and mouse. The presence of YCAY clusters in lower vertebrates invariably predicted conservation of brain-specific splicing across species, whereas their absence in lower vertebrates correlated with a loss of alternative splicing. We hypothesize that evolution of Nova-regulated splicing in higher vertebrates proceeds mainly through changes in cis-acting elements, that tissue-specific splicing might in some cases evolve in a single step corresponding to evolution of a YCAY cluster, and that the conservation level of YCAY clusters relates to the functions encoded by the regulated RNAs.  (+info)

Amyloid-beta oligomers impair fear conditioned memory in a calcineurin-dependent fashion in mice. (2/71)


Mechanisms of AD neurodegeneration may be independent of Abeta and its derivatives. (3/71)


Glutamate carboxypeptidase II: an amyloid peptide-degrading enzyme with physiological function in the brain. (4/71)


The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease. (5/71)


Report of the task force on designing clinical trials in early (predementia) AD. (6/71)


Sulfated glycosaminoglycans accelerate transthyretin amyloidogenesis by quaternary structural conversion. (7/71)


Novel CHST6 gene mutations in 2 unrelated cases of macular corneal dystrophy. (8/71)


Amyloidogenic proteins are misfolded proteins that can form amyloid fibrils, which are insoluble protein aggregates with a characteristic cross-beta sheet quaternary structure. These amyloid fibrils can accumulate in various tissues and organs, leading to the formation of amyloid deposits. The accumulation of amyloidogenic proteins and the resulting amyloid deposits have been associated with several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as systemic amyloidoses.

In Alzheimer's disease, for example, the amyloidogenic protein is beta-amyloid, which is produced from the proteolytic processing of the amyloid precursor protein (APP). In Parkinson's disease, the amyloidogenic protein is alpha-synuclein, which forms the main component of Lewy bodies.

It's important to note that not all misfolded proteins are necessarily amyloidogenic, and not all amyloid fibrils are associated with disease. Some amyloid fibrils can have functional roles in normal physiological processes.

Amyloid is a term used in medicine to describe abnormally folded protein deposits that can accumulate in various tissues and organs of the body. These misfolded proteins can form aggregates known as amyloid fibrils, which have a characteristic beta-pleated sheet structure. Amyloid deposits can be composed of different types of proteins, depending on the specific disease associated with the deposit.

In some cases, amyloid deposits can cause damage to organs and tissues, leading to various clinical symptoms. Some examples of diseases associated with amyloidosis include Alzheimer's disease (where amyloid-beta protein accumulates in the brain), systemic amyloidosis (where amyloid fibrils deposit in various organs such as the heart, kidneys, and liver), and type 2 diabetes (where amyloid deposits form in the pancreas).

It's important to note that not all amyloid deposits are harmful or associated with disease. However, when they do cause problems, treatment typically involves managing the underlying condition that is leading to the abnormal protein accumulation.

Amyloidosis is a medical condition characterized by the abnormal accumulation of insoluble proteins called amyloid in various tissues and organs throughout the body. These misfolded protein deposits can disrupt the normal function of affected organs, leading to a range of symptoms depending on the location and extent of the amyloid deposition.

There are different types of amyloidosis, classified based on the specific proteins involved:

1. Primary (AL) Amyloidosis: This is the most common form, accounting for around 80% of cases. It results from the overproduction and misfolding of immunoglobulin light chains, typically by clonal plasma cells in the bone marrow. The amyloid deposits can affect various organs, including the heart, kidneys, liver, and nervous system.
2. Secondary (AA) Amyloidosis: This form is associated with chronic inflammatory diseases, such as rheumatoid arthritis, tuberculosis, or familial Mediterranean fever. The amyloid fibrils are composed of serum amyloid A protein (SAA), an acute-phase reactant produced during the inflammatory response. The kidneys are commonly affected in this type of amyloidosis.
3. Hereditary or Familial Amyloidosis: These forms are caused by genetic mutations that result in the production of abnormal proteins prone to misfolding and amyloid formation. Examples include transthyretin (TTR) amyloidosis, fibrinogen amyloidosis, and apolipoprotein AI amyloidosis. These forms can affect various organs, including the heart, nerves, and kidneys.
4. Dialysis-Related Amyloidosis: This form is seen in patients undergoing long-term dialysis for chronic kidney disease. The amyloid fibrils are composed of beta-2 microglobulin, a protein that accumulates due to impaired clearance during dialysis. The joints and bones are commonly affected in this type of amyloidosis.

The diagnosis of amyloidosis typically involves a combination of clinical evaluation, imaging studies, and tissue biopsy with the demonstration of amyloid deposition using special stains (e.g., Congo red). Treatment depends on the specific type and extent of organ involvement and may include supportive care, medications to target the underlying cause (e.g., chemotherapy, immunomodulatory agents), and organ transplantation in some cases.

Prealbumin, also known as transthyretin, is a protein produced primarily in the liver and circulates in the blood. It plays a role in transporting thyroid hormones and vitamin A throughout the body. Prealbumin levels are often used as an indicator of nutritional status and liver function. Low prealbumin levels may suggest malnutrition or inflammation, while increased levels can be seen in certain conditions like hyperthyroidism. It is important to note that prealbumin levels should be interpreted in conjunction with other clinical findings and laboratory tests for a more accurate assessment of a patient's health status.

Islet Amyloid Polypeptide (IAPP), also known as amylin, is a 37-amino acid peptide co-secreted with insulin from pancreatic beta-cells in response to meals. It plays crucial roles in regulating glucose homeostasis by suppressing glucagon secretion, slowing gastric emptying, and promoting satiety. In type 2 diabetes, IAPP can form amyloid fibrils, which deposit in pancreatic islets, contributing to beta-cell dysfunction and death. This contributes to the progressive nature of type 2 diabetes.

Congo Red is a synthetic diazo dye that is commonly used in histology and pathology for stainings and tests. It is particularly useful in identifying amyloid deposits in tissues, which are associated with various diseases such as Alzheimer's disease, type 2 diabetes, and systemic amyloidosis.

When Congo Red binds to amyloid fibrils, it exhibits a characteristic apple-green birefringence under polarized light microscopy. Additionally, Congo Red stained amyloid deposits show a shift in their emission spectrum when excited with circularly polarized light, a phenomenon known as dichroism. These properties make Congo Red a valuable tool for the diagnosis and study of amyloidosis and other protein misfolding disorders.

It is important to note that Congo Red staining should be performed with care, as it can be toxic and carcinogenic if not handled properly.

Amyloid beta-peptides (Aβ) are small protein fragments that are crucially involved in the pathogenesis of Alzheimer's disease. They are derived from a larger transmembrane protein called the amyloid precursor protein (APP) through a series of proteolytic cleavage events.

The two primary forms of Aβ peptides are Aβ40 and Aβ42, which differ in length by two amino acids. While both forms can be harmful, Aβ42 is more prone to aggregation and is considered to be the more pathogenic form. These peptides have the tendency to misfold and accumulate into oligomers, fibrils, and eventually insoluble plaques that deposit in various areas of the brain, most notably the cerebral cortex and hippocampus.

The accumulation of Aβ peptides is believed to initiate a cascade of events leading to neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal death, which are all hallmarks of Alzheimer's disease. Although the exact role of Aβ in the onset and progression of Alzheimer's is still under investigation, it is widely accepted that they play a central part in the development of this debilitating neurodegenerative disorder.

Protein folding is the process by which a protein molecule naturally folds into its three-dimensional structure, following the synthesis of its amino acid chain. This complex process is determined by the sequence and properties of the amino acids, as well as various environmental factors such as temperature, pH, and the presence of molecular chaperones. The final folded conformation of a protein is crucial for its proper function, as it enables the formation of specific interactions between different parts of the molecule, which in turn define its biological activity. Protein misfolding can lead to various diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

Beta-2 microglobulin (β2M) is a small protein that is a component of the major histocompatibility complex class I molecule, which plays a crucial role in the immune system. It is found on the surface of almost all nucleated cells in the body and is involved in presenting intracellular peptides to T-cells for immune surveillance.

β2M is produced at a relatively constant rate by cells throughout the body and is freely filtered by the glomeruli in the kidneys. Under normal circumstances, most of the filtrated β2M is reabsorbed and catabolized in the proximal tubules of the nephrons. However, when the glomerular filtration rate (GFR) is decreased, as in chronic kidney disease (CKD), the reabsorption capacity of the proximal tubules becomes overwhelmed, leading to increased levels of β2M in the blood and its subsequent appearance in the urine.

Elevated serum and urinary β2M levels have been associated with various clinical conditions, such as CKD, multiple myeloma, autoimmune disorders, and certain infectious diseases. Measuring β2M concentrations can provide valuable information for diagnostic, prognostic, and monitoring purposes in these contexts.

Prions are misfolded proteins that can induce other normal proteins to also adopt the misfolded shape, leading to the formation of aggregates. These abnormal prion protein aggregates are associated with a group of progressive neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). Examples of TSEs include bovine spongiform encephalopathy (BSE or "mad cow disease") in cattle, variant Creutzfeldt-Jakob disease (vCJD) in humans, and scrapie in sheep. The misfolded prion proteins are resistant to degradation by proteases, which contributes to their accumulation and subsequent neuronal damage, ultimately resulting in spongiform degeneration of the brain and other neurological symptoms associated with TSEs.

Secondary protein structure refers to the local spatial arrangement of amino acid chains in a protein, typically described as regular repeating patterns held together by hydrogen bonds. The two most common types of secondary structures are the alpha-helix (α-helix) and the beta-pleated sheet (β-sheet). In an α-helix, the polypeptide chain twists around itself in a helical shape, with each backbone atom forming a hydrogen bond with the fourth amino acid residue along the chain. This forms a rigid rod-like structure that is resistant to bending or twisting forces. In β-sheets, adjacent segments of the polypeptide chain run parallel or antiparallel to each other and are connected by hydrogen bonds, forming a pleated sheet-like arrangement. These secondary structures provide the foundation for the formation of tertiary and quaternary protein structures, which determine the overall three-dimensional shape and function of the protein.

Alpha-synuclein is a protein that is primarily found in neurons (nerve cells) in the brain. It is encoded by the SNCA gene and is abundantly expressed in presynaptic terminals, where it is believed to play a role in the regulation of neurotransmitter release.

In certain neurological disorders, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, alpha-synuclein can form aggregates known as Lewy bodies and Lewy neurites. These aggregates are a pathological hallmark of these diseases and are believed to contribute to the death of nerve cells, leading to the symptoms associated with these disorders.

The precise function of alpha-synuclein is not fully understood, but it is thought to be involved in various cellular processes such as maintaining the structure of the presynaptic terminal, regulating synaptic vesicle trafficking and neurotransmitter release, and protecting neurons from stress.

Quaternary protein structure refers to the arrangement and interaction of multiple folded protein molecules in a multi-subunit complex. These subunits can be identical or different forms of the same protein or distinctly different proteins that associate to form a functional complex. The quaternary structure is held together by non-covalent interactions, such as hydrogen bonds, ionic bonds, and van der Waals forces. Understanding quaternary structure is crucial for comprehending the function, regulation, and assembly of many protein complexes involved in various cellular processes.

Immunoglobulin light chains are the smaller protein subunits of an immunoglobulin, also known as an antibody. They are composed of two polypeptide chains, called kappa (κ) and lambda (λ), which are produced by B cells during the immune response. Each immunoglobulin molecule contains either two kappa or two lambda light chains, in association with two heavy chains.

Light chains play a crucial role in the antigen-binding site of an antibody, where they contribute to the specificity and affinity of the interaction between the antibody and its target antigen. In addition to their role in immune function, abnormal production or accumulation of light chains can lead to various diseases, such as multiple myeloma and amyloidosis.

Circular dichroism (CD) is a technique used in physics and chemistry to study the structure of molecules, particularly large biological molecules such as proteins and nucleic acids. It measures the difference in absorption of left-handed and right-handed circularly polarized light by a sample. This difference in absorption can provide information about the three-dimensional structure of the molecule, including its chirality or "handedness."

In more technical terms, CD is a form of spectroscopy that measures the differential absorption of left and right circularly polarized light as a function of wavelength. The CD signal is measured in units of millidegrees (mdeg) and can be positive or negative, depending on the type of chromophore and its orientation within the molecule.

CD spectra can provide valuable information about the secondary and tertiary structure of proteins, as well as the conformation of nucleic acids. For example, alpha-helical proteins typically exhibit a strong positive band near 190 nm and two negative bands at around 208 nm and 222 nm, while beta-sheet proteins show a strong positive band near 195 nm and two negative bands at around 217 nm and 175 nm.

CD spectroscopy is a powerful tool for studying the structural changes that occur in biological molecules under different conditions, such as temperature, pH, or the presence of ligands or other molecules. It can also be used to monitor the folding and unfolding of proteins, as well as the binding of drugs or other small molecules to their targets.

Protein multimerization refers to the process where multiple protein subunits assemble together to form a complex, repetitive structure called a multimer or oligomer. This can involve the association of identical or similar protein subunits through non-covalent interactions such as hydrogen bonding, ionic bonding, and van der Waals forces. The resulting multimeric structures can have various shapes, sizes, and functions, including enzymatic activity, transport, or structural support. Protein multimerization plays a crucial role in many biological processes and is often necessary for the proper functioning of proteins within cells.

Protein conformation refers to the specific three-dimensional shape that a protein molecule assumes due to the spatial arrangement of its constituent amino acid residues and their associated chemical groups. This complex structure is determined by several factors, including covalent bonds (disulfide bridges), hydrogen bonds, van der Waals forces, and ionic bonds, which help stabilize the protein's unique conformation.

Protein conformations can be broadly classified into two categories: primary, secondary, tertiary, and quaternary structures. The primary structure represents the linear sequence of amino acids in a polypeptide chain. The secondary structure arises from local interactions between adjacent amino acid residues, leading to the formation of recurring motifs such as α-helices and β-sheets. Tertiary structure refers to the overall three-dimensional folding pattern of a single polypeptide chain, while quaternary structure describes the spatial arrangement of multiple folded polypeptide chains (subunits) that interact to form a functional protein complex.

Understanding protein conformation is crucial for elucidating protein function, as the specific three-dimensional shape of a protein directly influences its ability to interact with other molecules, such as ligands, nucleic acids, or other proteins. Any alterations in protein conformation due to genetic mutations, environmental factors, or chemical modifications can lead to loss of function, misfolding, aggregation, and disease states like neurodegenerative disorders and cancer.

Neurodegenerative diseases are a group of disorders characterized by progressive and persistent loss of neuronal structure and function, often leading to cognitive decline, functional impairment, and ultimately death. These conditions are associated with the accumulation of abnormal protein aggregates, mitochondrial dysfunction, oxidative stress, chronic inflammation, and genetic mutations in the brain. Examples of neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), and Spinal Muscular Atrophy (SMA). The underlying causes and mechanisms of these diseases are not fully understood, and there is currently no cure for most neurodegenerative disorders. Treatment typically focuses on managing symptoms and slowing disease progression.

Transmission electron microscopy (TEM) is a type of microscopy in which an electron beam is transmitted through a ultra-thin specimen, interacting with it as it passes through. An image is formed from the interaction of the electrons with the specimen; the image is then magnified and visualized on a fluorescent screen or recorded on an electronic detector (or photographic film in older models).

TEM can provide high-resolution, high-magnification images that can reveal the internal structure of specimens including cells, viruses, and even molecules. It is widely used in biological and materials science research to investigate the ultrastructure of cells, tissues and materials. In medicine, TEM is used for diagnostic purposes in fields such as virology and bacteriology.

It's important to note that preparing a sample for TEM is a complex process, requiring specialized techniques to create thin (50-100 nm) specimens. These include cutting ultrathin sections of embedded samples using an ultramicrotome, staining with heavy metal salts, and positive staining or negative staining methods.

A peptide fragment is a short chain of amino acids that is derived from a larger peptide or protein through various biological or chemical processes. These fragments can result from the natural breakdown of proteins in the body during regular physiological processes, such as digestion, or they can be produced experimentally in a laboratory setting for research or therapeutic purposes.

Peptide fragments are often used in research to map the structure and function of larger peptides and proteins, as well as to study their interactions with other molecules. In some cases, peptide fragments may also have biological activity of their own and can be developed into drugs or diagnostic tools. For example, certain peptide fragments derived from hormones or neurotransmitters may bind to receptors in the body and mimic or block the effects of the full-length molecule.

Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. It's the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently.

The early signs of the disease include forgetting recent events or conversations. As the disease progresses, a person with Alzheimer's disease will develop severe memory impairment and lose the ability to carry out everyday tasks.

Currently, there's no cure for Alzheimer's disease. However, treatments can temporarily slow the worsening of dementia symptoms and improve quality of life.

The Amyloid Beta-Protein Precursor (AβPP) is a type of transmembrane protein that is widely expressed in various tissues and organs, including the brain. It plays a crucial role in normal physiological processes, such as neuronal development, synaptic plasticity, and repair.

AβPP undergoes proteolytic processing by enzymes called secretases, resulting in the production of several protein fragments, including the amyloid-beta (Aβ) peptide. Aβ is a small peptide that can aggregate and form insoluble fibrils, which are the main component of amyloid plaques found in the brains of patients with Alzheimer's disease (AD).

The accumulation of Aβ plaques is believed to contribute to the neurodegeneration and cognitive decline observed in AD. Therefore, AβPP and its proteolytic processing have been the focus of extensive research aimed at understanding the pathogenesis of AD and developing potential therapies.

Familial amyloidosis is a genetic disorder characterized by the buildup of abnormal protein deposits called amyloid fibrils in various tissues and organs throughout the body. These abnormal protein deposits can cause damage to the affected organs, leading to a variety of symptoms.

There are several types of familial amyloidosis, but the most common type is transthyretin-related hereditary amyloidosis (TTR-HA). This form of the disorder is caused by mutations in the TTR gene, which provides instructions for making a protein called transthyretin. Transthyretin is a transport protein that helps move thyroid hormones and vitamin A around the body. In TTR-HA, mutations in the TTR gene cause the transthyretin protein to misfold and form amyloid fibrils.

Symptoms of familial amyloidosis can vary widely depending on which organs are affected. Commonly affected organs include the heart, kidneys, nerves, and gastrointestinal tract. Symptoms may include:

* Heart problems such as arrhythmias (irregular heartbeat), heart failure, or cardiac conduction abnormalities
* Kidney problems such as proteinuria (protein in the urine) or kidney failure
* Nerve damage leading to numbness, tingling, or pain in the hands and feet, or autonomic nervous system dysfunction affecting digestion, bladder function, or blood pressure regulation
* Gastrointestinal problems such as diarrhea, constipation, nausea, vomiting, or abdominal pain

Familial amyloidosis is typically inherited in an autosomal dominant manner, meaning that a child has a 50% chance of inheriting the mutated gene from a parent with the disorder. However, some cases may be due to new (de novo) mutations and occur in people without a family history of the disorder.

Diagnosis of familial amyloidosis typically involves a combination of clinical evaluation, genetic testing, and tissue biopsy to confirm the presence of amyloid fibrils. Treatment may involve medications to manage symptoms, as well as liver transplantation or other experimental therapies aimed at reducing the production of abnormal proteins that form amyloid fibrils.

Fourier Transform Infrared (FTIR) spectroscopy is a type of infrared spectroscopy that uses the Fourier transform mathematical technique to convert the raw data obtained from an interferometer into a more interpretable spectrum. This technique allows for the simultaneous collection of a wide range of wavelengths, resulting in increased sensitivity and speed compared to traditional dispersive infrared spectroscopy.

FTIR spectroscopy measures the absorption or transmission of infrared radiation by a sample as a function of frequency, providing information about the vibrational modes of the molecules present in the sample. This can be used for identification and quantification of chemical compounds, analysis of molecular structure, and investigation of chemical interactions and reactions.

In summary, FTIR spectroscopy is a powerful analytical technique that uses infrared radiation to study the vibrational properties of molecules, with increased sensitivity and speed due to the use of Fourier transform mathematical techniques and an interferometer.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Peptides are short chains of amino acid residues linked by covalent bonds, known as peptide bonds. They are formed when two or more amino acids are joined together through a condensation reaction, which results in the elimination of a water molecule and the formation of an amide bond between the carboxyl group of one amino acid and the amino group of another.

Peptides can vary in length from two to about fifty amino acids, and they are often classified based on their size. For example, dipeptides contain two amino acids, tripeptides contain three, and so on. Oligopeptides typically contain up to ten amino acids, while polypeptides can contain dozens or even hundreds of amino acids.

Peptides play many important roles in the body, including serving as hormones, neurotransmitters, enzymes, and antibiotics. They are also used in medical research and therapeutic applications, such as drug delivery and tissue engineering.

Amyloid precursor protein (APP) secretases are enzymes that are responsible for cleaving the amyloid precursor protein into various smaller proteins. There are two types of APP secretases: α-secretase and β-secretase.

α-Secretase is a member of the ADAM (a disintegrin and metalloproteinase) family, specifically ADAM10 and ADAM17. When APP is cleaved by α-secretase, it produces a large ectodomain called sAPPα and a membrane-bound C-terminal fragment called C83. This pathway is known as the non-amyloidogenic pathway because it prevents the formation of amyloid-β (Aβ) peptides, which are associated with Alzheimer's disease.

β-Secretase, also known as β-site APP cleaving enzyme 1 (BACE1), is a type II transmembrane aspartic protease. When APP is cleaved by β-secretase, it produces a large ectodomain called sAPPβ and a membrane-bound C-terminal fragment called C99. Subsequently, C99 is further cleaved by γ-secretase to generate Aβ peptides, including the highly neurotoxic Aβ42. This pathway is known as the amyloidogenic pathway because it leads to the formation of Aβ peptides and the development of Alzheimer's disease.

Therefore, APP secretases play a crucial role in the regulation of APP processing and have been the focus of extensive research in the context of Alzheimer's disease and other neurodegenerative disorders.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Hydrogen-ion concentration, also known as pH, is a measure of the acidity or basicity of a solution. It is defined as the negative logarithm (to the base 10) of the hydrogen ion activity in a solution. The standard unit of measurement is the pH unit. A pH of 7 is neutral, less than 7 is acidic, and greater than 7 is basic.

In medical terms, hydrogen-ion concentration is important for maintaining homeostasis within the body. For example, in the stomach, a high hydrogen-ion concentration (low pH) is necessary for the digestion of food. However, in other parts of the body such as blood, a high hydrogen-ion concentration can be harmful and lead to acidosis. Conversely, a low hydrogen-ion concentration (high pH) in the blood can lead to alkalosis. Both acidosis and alkalosis can have serious consequences on various organ systems if not corrected.

Amyloid neuropathies are a group of peripheral nerve disorders caused by the abnormal accumulation of amyloid proteins in the nerves. Amyloid is a protein that can be produced in various diseases and can deposit in different organs, including nerves. When this occurs in the nerves, it can lead to damage and dysfunction, resulting in symptoms such as numbness, tingling, pain, and weakness in the affected limbs.

There are several types of amyloid neuropathies, with the two most common being:

1. Transthyretin (TTR)-related hereditary amyloidosis: This is an inherited disorder caused by mutations in the TTR gene, which leads to the production of abnormal TTR protein that can form amyloid deposits in various organs, including nerves.
2. Immunoglobulin light chain (AL) amyloidosis: This is a disorder in which abnormal plasma cells produce excessive amounts of immunoglobulin light chains, which can form amyloid deposits in various organs, including nerves.

The diagnosis of amyloid neuropathies typically involves a combination of clinical evaluation, nerve conduction studies, and tissue biopsy to confirm the presence of amyloid deposits. Treatment options depend on the underlying cause of the disorder and may include medications, chemotherapy, stem cell transplantation, or supportive care to manage symptoms.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Aspartic acid endopeptidases are a type of enzyme that cleave peptide bonds within proteins. They are also known as aspartyl proteases or aspartic proteinases. These enzymes contain two catalytic aspartic acid residues in their active site, which work together to hydrolyze the peptide bond.

Aspartic acid endopeptidases play important roles in various biological processes, including protein degradation, processing, and activation. They are found in many organisms, including viruses, bacteria, fungi, plants, and animals. Some well-known examples of aspartic acid endopeptidases include pepsin, cathepsin D, and HIV protease.

Pepsin is a digestive enzyme found in the stomach that helps break down proteins in food. Cathepsin D is a lysosomal enzyme that plays a role in protein turnover and degradation within cells. HIV protease is an essential enzyme for the replication of the human immunodeficiency virus (HIV), which causes AIDS. Inhibitors of HIV protease are used as antiretroviral drugs to treat HIV infection.

Amyloid plaque is a pathological hallmark of several degenerative diseases, including Alzheimer's disease. It refers to extracellular deposits of misfolded proteins that accumulate in various tissues and organs, but are most commonly found in the brain. The main component of these plaques is an abnormally folded form of a protein called amyloid-beta (Aβ). This protein is produced through the normal processing of the amyloid precursor protein (APP), but in amyloid plaques, it aggregates into insoluble fibrils that form the core of the plaque.

The accumulation of amyloid plaques is thought to contribute to neurodegeneration and cognitive decline in Alzheimer's disease and other related disorders. The exact mechanisms by which this occurs are not fully understood, but it is believed that the aggregation of Aβ into plaques leads to the disruption of neuronal function and viability, as well as the activation of inflammatory responses that can further damage brain tissue.

It's important to note that while amyloid plaques are a key feature of Alzheimer's disease, they are not exclusive to this condition. Amyloid plaques have also been found in other neurodegenerative disorders, as well as in some normal aging brains, although their significance in these contexts is less clear.

Familial amyloid neuropathies are a group of inherited disorders characterized by the accumulation of abnormal deposits of amyloid proteins in various tissues and organs of the body. These abnormal deposits can cause damage to nerves, leading to a peripheral neuropathy that affects sensation, movement, and organ function.

There are several types of familial amyloid neuropathies, each caused by different genetic mutations. The most common type is known as transthyretin-related hereditary amyloidosis (TTR-HA), which is caused by mutations in the TTR gene. Other types include apolipoprotein A1-related hereditary amyloidosis (APOA1-HA) and gelsolin-related amyloidosis (AGel-HA).

Symptoms of familial amyloid neuropathies can vary depending on the type and severity of the disorder. Common symptoms include:

* Numbness, tingling, or pain in the hands and feet
* Weakness or loss of muscle strength in the legs and arms
* Autonomic nervous system dysfunction, leading to problems with digestion, heart rate, blood pressure, and temperature regulation
* Carpal tunnel syndrome
* Eye abnormalities, such as vitreous opacities or retinal deposits
* Kidney disease

Familial amyloid neuropathies are typically inherited in an autosomal dominant manner, meaning that a child has a 50% chance of inheriting the mutated gene from an affected parent. Diagnosis is usually made through genetic testing and confirmation of the presence of amyloid deposits in tissue samples.

Treatment for familial amyloid neuropathies typically involves managing symptoms and slowing the progression of the disease. This may include medications to control pain, physical therapy to maintain muscle strength and mobility, and devices such as braces or wheelchairs to assist with mobility. In some cases, liver transplantation may be recommended to remove the source of the mutated transthyretin protein.

Atomic Force Microscopy (AFM) is a type of microscopy that allows visualization and measurement of surfaces at the atomic level. It works by using a sharp probe, called a tip, that is mounted on a flexible cantilever. The tip is brought very close to the surface of the sample and as the sample is scanned, the forces between the tip and the sample cause the cantilever to deflect. This deflection is measured and used to generate a topographic map of the surface with extremely high resolution, often on the order of fractions of a nanometer. AFM can be used to study both conductive and non-conductive samples, and can operate in various environments, including air and liquid. It has applications in fields such as materials science, biology, and chemistry.

Bence Jones protein is a type of immunoglobulin light chain that can be detected in the urine or blood of some patients with certain diseases, most notably multiple myeloma. It's named after Henry Bence Jones, a 19th-century English physician who first described it.

These proteins are produced by malignant plasma cells, which are a type of white blood cell found in the bone marrow. In multiple myeloma, these cancerous cells multiply and produce abnormal amounts of immunoglobulins, leading to the overproduction of Bence Jones proteins.

When these proteins are excreted in the urine, they can cause damage to the kidneys, leading to kidney dysfunction or failure. Therefore, the detection of Bence Jones protein in the urine can be a sign of multiple myeloma or other related diseases. However, it's important to note that not all patients with multiple myeloma will have Bence Jones proteins in their urine.

I believe there might be a slight confusion in your question. There is no medical definition for "Insulysin" as it seems to be a misspelling of the term "Insulinase" or "Insulysin." I will provide you with the medical definition of Insulinase.

Insulinase, also known as Insulin-degrading enzyme (IDE), is a zinc metalloproteinase found in various tissues, including the liver, brain, and muscle. It is responsible for the intracellular degradation of insulin and other regulatory proteins like amyloid-beta peptide, glucagon, and atrial natriuretic peptide. Insulinase helps regulate blood glucose levels by controlling insulin concentrations in the body. Dysregulation of this enzyme has been implicated in diabetes, Alzheimer's disease, and other neurodegenerative disorders.

Thiazoles are organic compounds that contain a heterocyclic ring consisting of a nitrogen atom and a sulfur atom, along with two carbon atoms and two hydrogen atoms. They have the chemical formula C3H4NS. Thiazoles are present in various natural and synthetic substances, including some vitamins, drugs, and dyes. In the context of medicine, thiazole derivatives have been developed as pharmaceuticals for their diverse biological activities, such as anti-inflammatory, antifungal, antibacterial, and antihypertensive properties. Some well-known examples include thiazide diuretics (e.g., hydrochlorothiazide) used to treat high blood pressure and edema, and the antidiabetic drug pioglitazone.

Neurofibrils are thin, thread-like structures found within the cytoplasm of nerve cells (neurons). They are primarily composed of various proteins and are involved in maintaining the structure and function of neurons. Neurofibrils include two types: neurofilaments and microtubule-associated protein tau (TAU) proteins.

Neurofilaments are intermediate filaments that provide structural support to neurons, while TAU proteins are involved in microtubule assembly, stability, and intracellular transport. Abnormal accumulation and aggregation of these proteins can lead to neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

Hydrophobic interactions: These are the interactions that occur between non-polar molecules or groups of atoms in an aqueous environment, leading to their association or aggregation. The term "hydrophobic" means "water-fearing" and describes the tendency of non-polar substances to repel water. When non-polar molecules or groups are placed in water, they tend to clump together to minimize contact with the polar water molecules. These interactions are primarily driven by the entropy increase of the system as a whole, rather than energy minimization. Hydrophobic interactions play crucial roles in various biological processes, such as protein folding, membrane formation, and molecular self-assembly.

Hydrophilic interactions: These are the interactions that occur between polar molecules or groups of atoms and water molecules. The term "hydrophilic" means "water-loving" and describes the attraction of polar substances to water. When polar molecules or groups are placed in water, they can form hydrogen bonds with the surrounding water molecules, which helps solvate them. Hydrophilic interactions contribute to the stability and functionality of various biological systems, such as protein structure, ion transport across membranes, and enzyme catalysis.

Post-translational protein processing refers to the modifications and changes that proteins undergo after their synthesis on ribosomes, which are complex molecular machines responsible for protein synthesis. These modifications occur through various biochemical processes and play a crucial role in determining the final structure, function, and stability of the protein.

The process begins with the translation of messenger RNA (mRNA) into a linear polypeptide chain, which is then subjected to several post-translational modifications. These modifications can include:

1. Proteolytic cleavage: The removal of specific segments or domains from the polypeptide chain by proteases, resulting in the formation of mature, functional protein subunits.
2. Chemical modifications: Addition or modification of chemical groups to the side chains of amino acids, such as phosphorylation (addition of a phosphate group), glycosylation (addition of sugar moieties), methylation (addition of a methyl group), acetylation (addition of an acetyl group), and ubiquitination (addition of a ubiquitin protein).
3. Disulfide bond formation: The oxidation of specific cysteine residues within the polypeptide chain, leading to the formation of disulfide bonds between them. This process helps stabilize the three-dimensional structure of proteins, particularly in extracellular environments.
4. Folding and assembly: The acquisition of a specific three-dimensional conformation by the polypeptide chain, which is essential for its function. Chaperone proteins assist in this process to ensure proper folding and prevent aggregation.
5. Protein targeting: The directed transport of proteins to their appropriate cellular locations, such as the nucleus, mitochondria, endoplasmic reticulum, or plasma membrane. This is often facilitated by specific signal sequences within the protein that are recognized and bound by transport machinery.

Collectively, these post-translational modifications contribute to the functional diversity of proteins in living organisms, allowing them to perform a wide range of cellular processes, including signaling, catalysis, regulation, and structural support.

Muramidase, also known as lysozyme, is an enzyme that hydrolyzes the glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycan, a polymer found in bacterial cell walls. This enzymatic activity plays a crucial role in the innate immune system by contributing to the destruction of invading bacteria. Muramidase is widely distributed in various tissues and bodily fluids, such as tears, saliva, and milk, and is also found in several types of white blood cells, including neutrophils and monocytes.

Protein stability refers to the ability of a protein to maintain its native structure and function under various physiological conditions. It is determined by the balance between forces that promote a stable conformation, such as intramolecular interactions (hydrogen bonds, van der Waals forces, and hydrophobic effects), and those that destabilize it, such as thermal motion, chemical denaturation, and environmental factors like pH and salt concentration. A protein with high stability is more resistant to changes in its structure and function, even under harsh conditions, while a protein with low stability is more prone to unfolding or aggregation, which can lead to loss of function or disease states, such as protein misfolding diseases.

Serum Amyloid A (SAA) protein is an acute phase protein produced primarily in the liver, although it can also be produced by other cells in response to inflammation. It is a member of the apolipoprotein family and is found in high-density lipoproteins (HDL) in the blood. SAA protein levels increase rapidly during the acute phase response to infection, trauma, or tissue damage, making it a useful biomarker for inflammation.

In addition to its role as an acute phase protein, SAA has been implicated in several disease processes, including atherosclerosis and amyloidosis. In amyloidosis, SAA can form insoluble fibrils that deposit in various tissues, leading to organ dysfunction. There are four subtypes of SAA in humans (SAA1, SAA2, SAA3, and SAA4), with SAA1 and SAA2 being the most responsive to inflammatory stimuli.

Hydrogen bonding is not a medical term per se, but it is a fundamental concept in chemistry and biology that is relevant to the field of medicine. Here's a general definition:

Hydrogen bonding is a type of attractive force between molecules or within a molecule, which occurs when a hydrogen atom is bonded to a highly electronegative atom (like nitrogen, oxygen, or fluorine) and is then attracted to another electronegative atom. This attraction results in the formation of a partially covalent bond known as a "hydrogen bond."

In biological systems, hydrogen bonding plays a crucial role in the structure and function of many biomolecules, such as DNA, proteins, and carbohydrates. For example, the double helix structure of DNA is stabilized by hydrogen bonds between complementary base pairs (adenine-thymine and guanine-cytosine). Similarly, the three-dimensional structure of proteins is maintained by a network of hydrogen bonds that help to determine their function.

In medical contexts, hydrogen bonding can be relevant in understanding drug-receptor interactions, where hydrogen bonds between a drug molecule and its target protein can enhance the binding affinity and specificity of the interaction, leading to more effective therapeutic outcomes.

Endopeptidases are a type of enzyme that breaks down proteins by cleaving peptide bonds inside the polypeptide chain. They are also known as proteinases or endoproteinases. These enzymes work within the interior of the protein molecule, cutting it at specific points along its length, as opposed to exopeptidases, which remove individual amino acids from the ends of the protein chain.

Endopeptidases play a crucial role in various biological processes, such as digestion, blood coagulation, and programmed cell death (apoptosis). They are classified based on their catalytic mechanism and the structure of their active site. Some examples of endopeptidase families include serine proteases, cysteine proteases, aspartic proteases, and metalloproteases.

It is important to note that while endopeptidases are essential for normal physiological functions, they can also contribute to disease processes when their activity is unregulated or misdirected. For instance, excessive endopeptidase activity has been implicated in the pathogenesis of neurodegenerative disorders, cancer, and inflammatory conditions.

Protein denaturation is a process in which the native structure of a protein is altered, leading to loss of its biological activity. This can be caused by various factors such as changes in temperature, pH, or exposure to chemicals or radiation. The three-dimensional shape of a protein is crucial for its function, and denaturation causes the protein to lose this shape, resulting in impaired or complete loss of function. Denaturation is often irreversible and can lead to the aggregation of proteins, which can have negative effects on cellular function and can contribute to diseases such as Alzheimer's and Parkinson's.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Peptide termination factors, also known as release factors, are proteins involved in the process of protein biosynthesis in cells. Specifically, they play a crucial role in the termination step of translation, which is the process by which the genetic code in messenger RNA (mRNA) is translated into a specific sequence of amino acids to form a protein.

During translation, ribosomes move along the mRNA and read the codons (three-nucleotide sequences) to add the corresponding amino acids to the growing polypeptide chain. When the ribosome encounters a stop codon (UAA, UAG, or UGA), peptide termination factors recognize it and bind to the ribosome. The specific factor that recognizes each stop codon is called a class 1 release factor.

In eukaryotic cells, there are two main class 1 release factors: eRF1 (eukaryotic release factor 1) and eRF3. eRF1 recognizes all three stop codons and promotes the hydrolysis of the peptidyl-tRNA bond, releasing the completed polypeptide chain from the ribosome. eRF3 acts as a GTPase and interacts with eRF1 to facilitate its binding to the ribosome.

Once the polypeptide is released, the ribosome dissociates from the mRNA, allowing for another round of translation or degradation of the mRNA. Peptide termination factors are essential for accurate protein synthesis and preventing errors due to premature termination or readthrough of stop codons.

Protein unfolding, also known as protein denaturation, refers to the loss of a protein's native structure, leading to a random or disordered conformation. Proteins are complex molecules that fold into specific three-dimensional shapes, allowing them to perform their biological functions. Various factors, such as heat, changes in pH, chemical denaturants, or mechanical forces, can disrupt the delicate balance of interactions that maintain this folded structure, causing the protein to unfold. Unfolded proteins may lose their functionality and can aggregate, forming insoluble aggregates, which can be harmful to cells and contribute to various diseases, including neurodegenerative disorders.

Presenilin-1 (PSEN1) is a gene that provides instructions for making one part of an enzyme complex called gamma-secretase. This enzyme is involved in the breakdown of certain proteins, most notably the amyloid precursor protein (APP), into smaller fragments called peptides. One of these peptides, called beta-amyloid, can accumulate and form clumps called plaques, which are a characteristic feature of Alzheimer's disease.

Mutations in the PSEN1 gene have been identified as a major cause of early-onset familial Alzheimer's disease (FAD), a rare, inherited form of the disorder that usually develops before age 65. These mutations result in an abnormal gamma-secretase enzyme that produces more toxic beta-amyloid peptides and fewer harmless ones, leading to the formation of amyloid plaques and neurodegeneration.

It's important to note that while mutations in PSEN1 are associated with early-onset FAD, most cases of Alzheimer's disease are sporadic and develop later in life, typically after age 65. The role of PSEN1 and other genes associated with FAD in the more common, late-onset form of Alzheimer's is still being researched.

Presenilin-2 (PSEN2) is a protein that is encoded by the PSEN2 gene in humans. It is a member of the presenilin family, which are integral membrane proteins found in the endoplasmic reticulum and Golgi apparatus. Presenilin-2 is most well-known for its role in the processing of amyloid precursor protein (APP), which is implicated in the pathogenesis of Alzheimer's disease.

In the context of APP processing, presenilin-2 functions as a catalytic subunit of the gamma-secretase complex, which cleaves APP into smaller peptides, including the beta-amyloid peptide (Aβ). Mutations in the PSEN2 gene have been associated with early-onset familial Alzheimer's disease, suggesting that abnormal APP processing and Aβ accumulation play a significant role in the development of this disorder.

However, it is important to note that presenilin-2 has other functions beyond APP processing, including roles in cell signaling, calcium homeostasis, and autophagy. Dysregulation of these processes may also contribute to the pathogenesis of Alzheimer's disease and other neurodegenerative disorders.

I'm sorry for any confusion, but "thermodynamics" is not a term that has a specific medical definition. It is a branch of physics that deals with the relationships between heat and other forms of energy. However, the principles of thermodynamics can be applied to biological systems, including those in the human body, such as in the study of metabolism or muscle function. But in a medical context, "thermodynamics" would not be a term used independently as a diagnosis, treatment, or any medical condition.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

Giasson BI, Lee VM, Trojanowski JQ (2003). "Interactions of amyloidogenic proteins". Neuromolecular Medicine. 4 (1-2): 49-58. ... Look up tau protein or tau in Wiktionary, the free dictionary. tau+Proteins at the U.S. National Library of Medicine Medical ... The tau proteins were identified in 1975 as heat-stable proteins essential for microtubule assembly, and since then they have ... Tau protein has been shown to interact with: Alpha-synuclein, FYN, Proto-oncogene tyrosine-protein kinase Src S100B, and YWHAZ ...
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FAP is characterized by the systemic deposition of amyloidogenic variants of the transthyretin protein, especially in the ... "Novel methods for detecting amyloidogenic proteins in transthyretin related amyloidosis". Frontiers in Bioscience. 13 (13): ... The transthyretin protein is a tetramer. The tetramer has to dissociate into misfolded monomers to aggregate into a variety of ... Researchers reported mild adverse events and decreases in serum misfolded transthyretin protein concentrations through targeted ...
Vetrivel KS, Thinakaran G (Jan 2006). "Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments ... Amyloid-beta precursor protein is an ancient and highly conserved protein. In humans, the gene APP is located on chromosome 21 ... Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses ... Chauhan VP, Ray I, Chauhan A, Wisniewski HM (May 1999). "Binding of gelsolin, a secretory protein, to amyloid beta-protein". ...
... an amyloidogenic protein, dimerizes through three-dimensional domain swapping". Nature Structural Biology. 8 (4): 316-320. doi: ... In a proteomic study, Grubb and coworkers studied the plasma levels of 2893 proteins and found that cystatin C was the one with ... He also determined the amino acid sequence of the protein's single polypeptide chain and the secondary and 3D-structure of the ... Grubb and coworkers isolated a protein previously described to be present in urine and spinal fluid, but without known ...
April 2001). "Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping". Nature ... an amyloidogenic protein, dimerizes through three-dimensional domain swapping" (PDF). Nature Structural Biology. 8 (4): 316-20 ... it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes). Cystatin C belongs to ... Cystatin C was first described as 'gamma-trace' in 1961 as a trace protein together with other ones (such as beta-trace) in the ...
"Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease". The Journal of ... Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of ... The PD-1 protein in humans is encoded by the PDCD1 gene. PD-1 is a cell surface receptor that belongs to the immunoglobulin ... PD-L1 protein is upregulated on macrophages and dendritic cells (DC) in response to LPS and GM-CSF treatment, and on T cells ...
2001). "Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping" (PDF). Nat. Struct. ... Cystatin-SA is a protein that in humans is encoded by the CST2 gene. The cystatin superfamily encompasses proteins that contain ... 1984). "Protein inhibitors of cysteine proteinases. III. Amino-acid sequence of cystatin from chicken egg white". Hoppe- ... The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, ...
Liu T, Bitan G (March 2012). "Modulating self-assembly of amyloidogenic proteins as a therapeutic approach for ... Oxidative stress can directly cause neuron cell death or it can trigger a cascade of events that leads to protein misfolding, ... April 2012). "G-protein-coupled receptor 30 mediates rapid neuroprotective effects of estrogen via depression of NR2B- ... heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. Lithium has been shown to reduce ...
... it has been speculated to play a role in amyloid disease and it was found to be a stable form for amyloidogenic proteins in ... Notably, the protein lysozyme is among the few native-state proteins shown to contain an alpha-strand region; lysozyme from ... 2008). The geometry of alpha-sheet: Implications for its possible function as amyloid precursor in proteins Proteins 71:425-431 ... prion proteins, and transthyretin repeats, all of which are associated with protein misfolding disease. For example, amyloid ...
Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 ( ... After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is digested by γ-secretase. The ... The gp100 protein contains differentiation antigens.[2], and has been widely studied to be used as a target for melanoma ... Overview of all the structural information available in the PDB for UniProt: P40967 (Melanocyte protein PMEL) at the PDBe-KB. v ...
... will cleave amyloid-beta precursor protein (APP) into various types of amyloid beta (Aβ) protein. Most β-secretase activity ... CSF BACE1 activity could be a potential candidate biomarker to monitor amyloidogenic APP metabolism in the CNS. APP is an ... When Aβ peptide is released by proteolytic cleavage of amyloid-beta precursor protein, some Aβ peptides that are solubilized ... Amyloid plaque Aβ protein species ends in residue 40 or 42, but it is suspected that Aβ42 form is crucial in the pathogenesis ...
... amyloidogenic properties of PrP and known fungal proteins. As in yeast, proteins involved in gene expression and RNA binding ... One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of ... While asserting that the flow of sequence information from protein to protein, or from protein to RNA and DNA was "precluded", ... In yeast, protein refolding to the prion configuration is assisted by chaperone proteins such as Hsp104. All known prions ...
Rhoades studies intrinsically disordered proteins and amyloidogenic proteins involved in Parkinson's disease, Alzheimer's ... focusing on understanding structural plasticity in intrinsically disordered proteins. These proteins do not form stable ... Rhoades E, Cohen M, Schuler B, Haran G (November 2004). "Two-state folding observed in individual protein molecules". J. Am. ... Research in the Rhoades lab aims to elucidate the principles that link protein conformational change with structure-function ...
... localization in human cerebral cortex and generation of amyloidogenic fragments from the beta-amyloid precursor protein". ... Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the ... Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF (July 1989). "Antibiotic proteins of human ... Cathepsin G is a 255-amino-acid-residue protein including an 18-residue signal peptide, a two-residue activation peptide at the ...
Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" - from the test tube to animal ... Examples include the proteins involved in Alzheimer's disease - amyloid β-protein (Aβ) and tau; α-synuclein, which is thought ... efficiently inhibit the formation of toxic oligomers and aggregates by amyloidogenic proteins associated with different ... aggregation-prone mutants of the tumor-suppressor protein p53; and semen proteins whose aggregation enhances HIV infection. ...
It is associated with the systemic production and release of many amyloidogenic proteins, especially immunoglobulin light chain ... Amyloidosis and Other Protein Deposition Diseases", Emery and Rimoin's Principles and Practice of Medical Genetics, Oxford: ... Infiltrative and Protein Misfolding Myocardial Diseases", Muscle, Boston/Waltham: Academic Press, pp. 625-637, doi:10.1016/b978 ... diastolic dysfunction congestive heart failure arrythmia cardiac nervous conduction block fatigue dyspnea Amyloid proteins are ...
... a metalloprotease from Alzheimer's disease brain able to degrade the beta-amyloid precursor protein and generate amyloidogenic ... 2001). "The neuropeptide processing enzyme EC is modulated by protein kinase A phosphorylation". J. Biol. Chem. 275 ( ... Lehner B, Sanderson CM (2004). "A Protein Interaction Framework for Human mRNA Degradation". Genome Res. 14 (7): 1315-23. doi: ...
... have also been implicated in similar maturation events for other transmembrane proteins such as MHC class I proteins. Recent ... Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway ... "Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the ... Other ADAM proteins, ADAM17 (also called TACE, tumor necrosis factor-α converting enzyme), ADAM9, and ADAM19 have also been ...
Amyloidogenic proteins, such as the Huntingtin protein, are the IPOD's substrates.[citation needed] Misfolded proteins must be ... Structural proteins, Huntington's disease, Proteins, Protein complexes, Protein structure, Organelles, Microscopy, Fluorescence ... The IPOD was shown to be the sub-cellular site to which toxic amyloidogenic proteins are sequestered to, hereby serving as a ... For many years, protein aggregation was considered a random process by which misfolded proteins stick to each other to form ...
Also, the IPOD is the sub-cellular site to which amyloidogenic proteins are sequestered in yeast, and where prions like [PSI+] ... When a reporter protein is fused with a prion domain, it forms a chimeric protein that demonstrates the conformational ... This transmission of protein state represents an epigenetic phenomenon where information is encoded in the protein structure ... cells is due to a reduced amount of functional Sup35 because much of the protein is in the amyloid state. The Sup35 protein ...
... is formed from the Danish mutant protein (BRI2-ADan), which exhibits amyloidogenic features. ADan causes amyloid angiopathy in ... In healthy people, BRI2 is produced as an immature type-II membrane protein (imBRI2), which is cleaved at the C-terminus by a ... pro-protein convertase to create mature BRI2 (mBRI2) and a 23aa soluble C-terminal fragment (Bri23). However, in FDD patients, ...
It also inhibits production of amyloidogenic A beta peptide and increases secretion of soluble amyloid precursor protein via ...
One major research focus is the role of protein misfolding in the onset of amyloidogenic diseases, including dialysis-related ... Proteins in this outer membrane facilitate transport with the outside world. These proteins share a similar nanoscale structure ... "Pore-like proteins designed from scratch". EurekAlert!. Retrieved 14 March 2021. "Pore-like proteins designed from scratch". ... "Protein-protein interactions in the early stages of amyloid assembly mechanisms". Wellcome. Retrieved 14 March 2021. "' ...
In tissue culture, the enzyme has been found to generate amyloidogenic fragments from the amyloid precursor protein, suggesting ... Kallikrein-6 is a protein that in humans is encoded by the KLK6 gene. Kallikrein-6 is also referred to as neurosin, protease M ... Thus, degradation of this protein is necessary to prevent infection. In mice brain samples, protease inhibitors were used to ... As a degradation enzyme, it has the capability of degrading extracellular matrix proteins on both normal and malignant cells, ...
... was used to accurately predict which regions of amyloidogenic proteins were most likely to make amyloid-like fibrils. By taking ... Rosetta@home aims to predict protein-protein docking and design new proteins with the help of about fifty-five thousand active ... July 2003). "Protein-protein docking predictions for the CAPRI experiment". Proteins. 52 (1): 118-22. CiteSeerX ... Wang C, Schueler-Furman O, Baker D (May 2005). "Improved side-chain modeling for protein-protein docking". Protein Science. 14 ...
Deposition patterns vary between people but are almost always composed of just one amyloidogenic protein. Deposition can be ... Within these 36 proteins, 19 are grouped into localized forms, 14 are grouped as systemic forms, and 3 proteins can identify as ... All amyloid fibril proteins start with the letter "A" followed by the protein suffix (and any applicable specification). See ... The type of the amyloid protein can be determined in various ways: the detection of abnormal proteins in the bloodstream (on ...
Production and increased detection of amyloid protein and amyloidogenic fragments in brain microvessels, meningeal vessels and ... "Production and increased detection of amyloid protein and amyloidogenic fragments in brain microvessels, meningeal vessels and ...
Identification of NEEP21 as a β-Amyloid Precursor Protein-Interacting Protein In Vivo That Modulates Amyloidogenic Processing ... Identification of NEEP21 as a β-Amyloid Precursor Protein-Interacting Protein In Vivo That Modulates Amyloidogenic Processing ... Identification of NEEP21 as a β-Amyloid Precursor Protein-Interacting Protein In Vivo That Modulates Amyloidogenic Processing ... Identification of NEEP21 as a β-Amyloid Precursor Protein-Interacting Protein In Vivo That Modulates Amyloidogenic Processing ...
This approach distinguishes oligomerization patterns of amyloidogenic and nonamyloidogenic proteins, allows quantification of ... For the amyloid beta-protein (Abeta), a consensus about the size and relative abundance of small oligomers has not been ... We describe here the application of the method Photoinduced Cross-Linking of Unmodified Proteins (PICUP) to the study of Abeta ... PICUP thus is a powerful tool for the investigation of small, metastable protein oligomers. The method provides essential ...
Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes Bhardwaj T., Gadhave K., Kapuganti S., Kumar P., Brotzakis ZF ...
Giasson BI, Lee VM, Trojanowski JQ (2003). "Interactions of amyloidogenic proteins". Neuromolecular Medicine. 4 (1-2): 49-58. ... Look up tau protein or tau in Wiktionary, the free dictionary. tau+Proteins at the U.S. National Library of Medicine Medical ... The tau proteins were identified in 1975 as heat-stable proteins essential for microtubule assembly, and since then they have ... Tau protein has been shown to interact with: Alpha-synuclein, FYN, Proto-oncogene tyrosine-protein kinase Src S100B, and YWHAZ ...
Amyloidogenic Proteins / chemical synthesis* * Amyloidogenic Proteins / chemistry * Animals * Humans Substances * Amyloid beta- ... Our model can be applied to other proteins and peptides as well. According to this model, the main building unit for the ... 1 Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia. [email protected] ... This mechanism of generation of amyloid fibrils may be common for other proteins and peptides. ...
Study of amyloidogenic polypeptides. Amyloid fibrils are associated with a number of human diseases, including Alzheimers and ... A theoretical study of the stability of disulfide bridges in various β-sheet structures of protein segment models Chem. Phys. ... Phosphorylation as Conformational Switch from the Native to Amyloid State: Trp-Cage as a Protein Aggregation Model J. Phys. ... MTA-ELTE Protein. Model. Res. Group. and. Laboratory of Structural. Chemistry and Biology * Home ...
Structural characterisation of amyloidogenic intrinsically disordered zinc finger protein isoforms DPF3b and DPF3a. ...
A fluorescence-based assay is used to screen cyclic peptides for their activity in preventing protein misfolding, an event that ... Protein misfolding and aggregation are common pathological features of several human diseases, including Alzheimers disease ... an integrated and generalizable bacterial system for the facile discovery of chemical rescuers of disease-associated protein ... are biosynthesized in Escherichia coli cells and simultaneously screened for their ability to rescue pathogenic protein ...
33, 34] Both are amyloidogenic.. In general, protein aggregation ensues from the binding of unfolded and misfolded polypeptides ... Protein folding in the endoplasmic reticulum and the unfolded protein response. Handb Exp Pharmacol. 2006. 69-91. [QxMD MEDLINE ... Accumulation of unfolded or misfolded proteins in the ER triggers the unfolded protein response (UPR), which is a survival ... the normal cellular isoform of prion protein (PrPc), and many other characteristic proteins. [33, 34, 35] Two major types of ...
... although all depend on hormone-mediated protein interactions. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates ... Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi- ... The jasmonate receptor is a three-molecule complex consisting of the F-box protein COI1, a JAZ (JASMONATE ZIM DOMAIN) ... The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation ...
Cell Surface Events in the Amyloidogenic Processing of the Amyloid Precursor Protein. Advisor: Dennis Selkoe. ... G Protein Regulation of Inwardly Rectifying Potassium Channels. Advisor: David Clapham. Shen, Jun. Using Forward and Reverse ... Protein Targeting in Neurons. Advisor: Kathleen Buckley. 1997. Bruce, Ashley. Characterization of an orthodenticle Homolog in ... Roles of centrosome proteins associated with primary microcephaly in mammalian corticogenesis. Advisor: Li-Huei Tsai. ...
Retention of amyloidogenic protein remains a key factor in patients on dialysis. Several factors affecting retention have been ... Davankov V, Pavlova L, Tsyurupa M, Brady J, Balsamo M, Yousha E. Polymeric adsorbent for removing toxic proteins from blood of ... Retention and accumulation of this type of amyloid protein is presumed to be the main pathogenic process underlying beta-2m ... This makes them impermeable to beta-2m, elevating the proteins serum levels. The newer cellulose triacetate dialyzers and the ...
Conformational evolution of molecular signatures during Amyloi-dogenic protein aggregation George Devitt, ...
Proteins (Proteins, Gene)IBA 03/2012 - 07/2007. 1. Amyloidogenic ProteinsIBA 01/2015. ...
Amyloidogenic proteins in Alzheimers disease and Parkinsons disease: interaction with chaperones and inflammation. ... Exploring proteins and microRNAs as biomarkers for differential diagnosis. 212. Spronk, D.B. (2016) Individual differences in ... Genes and protein networks for neurodevelopmental disorders. 72. Mädebach, A. (2011). Lexical access in speaking: Studies on ... The interaction of heparan sulfate proteoglycans with the amyloid b protein. 44. Qin, S.(2010) Adaptive memory: imaging medial ...
SARS-CoV-2 Spike Protein Interactions with Amyloidogenic Proteins: Potential Clues to Neurodegeneration. Biochem Biophys Res ... The Spike Protein is Toxic. The COVID-19 vaccines are all based on supplying genetic code to produce the spike protein that is ... PrP is the name given to the specific prion protein associated with these TSEs. Misfolded PrP proteins act as a seed or ... This also prevents the protein from fusing with the plasma membrane of a host cell. Id imagine that the spike protein attaches ...
Interactions of amyloidogenic proteins. Neuromolecular Medicine. 4: 49-58. PMID 14528052 DOI: 10.1385/Nmm:4:1-2:49 0.688. ... The ER retention protein RER1 promotes alpha-synuclein degradation via the proteasome. Plos One. 12: e0184262. PMID 28877262 ... Studies of protein aggregation in A53T α-synuclein transgenic, Tg2576 transgenic, and P246L presenilin-1 knock-in cross bred ... Nitration of tau protein is linked to neurodegeneration in tauopathies. The American Journal of Pathology. 163: 1021-31. PMID ...
Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity. Sci Rep. 2016 Sep 14; ... As such, we describe a general phenomenon by which viruses bind proteins in their coronas, leading to protein concentration and ... Nucleation of protein fibrillation by nanoparticles. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8691-6. PubMed. ... News: When Host Proteins Coat Virus, Amyloid Fibrils Form In response to Kariem Ezzat, wed like to note that, having looked at ...
... engineer or evolve substrate-optimized Hsp104 variants that attack select amyloidogenic proteins; and (3) generate Hsp104 or ... We have learned to stably perturb ER protein folding by converting an unfolded protein sensor called Ire1 into a finely ... Whereas other enveloped viruses use a single protein to effect cell entry, all herpesviruses require at least three proteins: ... DICER1 knockdown in glioblastoma cells increased cell growth and upregulated Cdk6 protein expression. Importantly, Cdk6 protein ...
Lack of Tau Proteins Rescues Neuronal Cell Death and Decreases Amyloidogenic Processing of APP in APP/PS1 Mice.. In: The ... Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a ... Erratum : amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires ... Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a ...
APP encodes amyloid precursor protein, a transmembrane protein which is cleaved to form amyloidogenic Aβ peptides. Mutations in ... MAPT encodes the microtubule associated protein tau, a protein central to Alzheimers disease neuropathology. MAPT mutations ... Navigate the proteins multiple functional domains and use the filter to home in on variants predicted to be moderately or ...
Amyloidogenic Proteins/metabolism * Apolipoprotein E4/genetics * Cognitive Reserve * Female * Follow-Up Studies ...
Mapping cellular response to destabilized transthyretin reveals cell- and amyloidogenic protein-specific signatures. Amyloid. ... The protein organization of a red blood cell. Cell Rep. 2022 Jul 19; 40(3):111103. PMID: 35858567. ...
... including the analyses of protein expression profiles, protein interaction networks and post-translational modifications) are ... In AL (amyloid light chain) amyloidosis, the most common form in Western countries, the amyloidogenic precursor is a misfolding ... Due to the primary role that proteins play in the pathogenesis of amyloidoses, mass spectrometry (MS)-based proteomic studies ... The cell line and/or tumor tissue secretome represents a valuable resource for discovering novel protein markers secreted by ...
... protein clearance and anti-amyloidogenic potentials of algal meta... ... This family of proteins consists of six separate members, which exist only in vertebrates. The architecture of CCN proteins is ... This family of proteins consists of six separate members in mammals. The architecture of CCN proteins is multimodular and ... protein clearance and anti-amyloidogenic potentials of a... ... p53 has been implicated as a tumor suppressor protein that has ...
Non-steroidal anti-inflammatory drugs stimulate secretion of non-amyloidogenic precursor protein. Avramovich, Y., Amit, T., ... Modulation of nuclear factor-kappa B activity by indomethacin influences A beta levels but not A beta precursor protein ... Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive ... was modulated by inhibitors of protein kinase C and Erk mitogen-activated protein (MAP) kinase [27]. ...
Amyloidogenic bacterial products, especially functional bacterial amyloid proteins, biosurfactants and endotoxins are possible ... such as the catabolite repressor/activator protein Cra, the cAMP receptor protein CRP, the protein RcdA (Brown et al., 2001; ... transient protein-protein interactions between distinct amyloid proteins and native alpha-synuclein can result in the formation ... 2007). The curli nucleator protein, CsgB, contains an amyloidogenic domain that directs CsgA polymerization. Proceedings of the ...
  • We showed that Trp-cage miniprotein and its variants are indeed a realistic model of larger globular systems of composite folding and aggregation landscapes and helps us to understand the fundamentals of protein aggregation and amyloid formation. (
  • Protein misfolding and aggregation are common pathological features of several human diseases, including Alzheimer's disease and type 2 diabetes. (
  • In this system, large combinatorial libraries of macrocyclic molecules are biosynthesized in Escherichia coli cells and simultaneously screened for their ability to rescue pathogenic protein misfolding and aggregation using a flow cytometric assay. (
  • The viral protein corona directs viral pathogenesis and amyloid aggregation. (
  • Amyloidosis is a group of diseases characterized by abnormal aggregation of proteins to form amyloid fibrils, and subsequent deposition in various tissues and organs, which can lead to severe functional failures. (
  • In in vitro experiments, curcumin has been shown to suppress the aggregation and cytotoxicity of Aβ, αSyn, islet amyloid precursor protein, ATTR, and prion protein ( Stefani and Rigacci, 2013 ). (
  • Furthermore, the S87A mutant, which was designed to block phosphorylation, exhibited a similar structure and similar membrane binding and aggregation properties as the wild-type (WT) protein. (
  • We demonstrated that 13 weeks post-injection, the overexpression of WT and S87A α-syn induced protein aggregation, dystrophic fiber formation, and a significant loss of dopaminergic neurons in vivo . (
  • Here we revisit tau protein aggregation at primary, secondary, tertiary and quaternary structures. (
  • In a second study, published October 23 online ahead of print by the journal Chemistry and Biology , Wiseman and his team asked if ATF6 activation could be similarly used to reduce secretion and aggregation of transthyretin-a protein that aggregates in association with other systemic amyloid diseases referred to as the transthyretin amyloidoses. (
  • While the binding did not to appear to affect protein conformations in solution, extended incubation of the amyloidogenic variants in the presence of different ECM components resulted in different aggregation propensity and aggregation patterns. (
  • A number of normal (wild-type) and mutant proteins are susceptible to such misfolding and aggregation (amyloidogenic proteins), thus accounting for the wide variety of causes and types of amyloidosis. (
  • Misfolding and aggregation of cellular prion protein (PrPc) is a major molecular process involved in the pathogenesis of prion diseases. (
  • However, recent evidence suggests that soluble protein oligomers, which are precursors for amyloid fibrils, are the primary toxic effectors responsible for the disease process. (
  • This mechanism of generation of amyloid fibrils may be common for other proteins and peptides. (
  • [9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. (
  • Apolipoprotein A-I (ApoA-I) amyloidosis is a rare protein misfolding disease where fibrils of the N-terminal domain of the protein accumulate in several organs, leading to their failure. (
  • Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. (
  • Amyloid fibrils are made of normally soluble misfolded proteins that aggregate into oligomers and then insoluble fibrils. (
  • In this study, we have used cryo-electron microscopy to investigate the three-dimensional structure of amyloid fibrils from full-length hnRNPA1 protein. (
  • As a result, the tetramers break down into individual transthyretin proteins, which attach to each other in strands called fibrils. (
  • AD is pathologically characterized by the deposition of pathogenic Aβ peptides that are derived from larger integral membrane proteins, termed β-amyloid precursor proteins (APPs). (
  • Our model can be applied to other proteins and peptides as well. (
  • APP encodes amyloid precursor protein, a transmembrane protein which is cleaved to form amyloidogenic Aβ peptides. (
  • Modulation of the Conformational Space of SARS-CoV-2 RNA Quadruplex RG-1 by Cellular Components and the Amyloidogenic Peptides α-Synuclein and hIAPP. (
  • Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease are associated with tau proteins that have become hyperphosphorylated insoluble aggregates called neurofibrillary tangles. (
  • MAPT encodes the microtubule associated protein tau, a protein central to Alzheimer's disease neuropathology. (
  • Bayer TA, Cappai R, Masters CL, Beyreuther K, Multhaup G (1999) It all sticks together-the APP-related family of proteins and Alzheimer's disease. (
  • Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease , immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy . (
  • Altered levels of naturally occurring autoantibodies (nAbs) against disease-associated neuronal proteins have been reported for neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). (
  • Mapping cellular response to destabilized transthyretin reveals cell- and amyloidogenic protein-specific signatures. (
  • Transthyretin (TTR) is a protein present in human serum whose role is to transport thyroxine and retinol-binding proteins, and it is vital for behavior, cognition, nerve regeneration, and axonal growth. (
  • Transthyretin amyloidosis is a progressive condition characterized by the buildup of abnormal protein deposits called amyloids (amyloidosis) in the body's organs and tissues. (
  • The TTR gene provides instructions for making a protein called transthyretin. (
  • To transport retinol and thyroxine, four transthyretin proteins must attach (bind) to each other to form a four-protein unit (tetramer). (
  • The central nervous systems of humans and cattle alike are attacked by prions (abnormal insoluble amyloidogenic proteins) when they suffer from Creutzfeldt Jakob disease (CJD) or bovine spongiform encephalopathy (BSE). (
  • In the ER, proteins, such as immunoglobulin light chains, fold into structures that are then secreted into the blood where they perform important functions in the body. (
  • In light chain amyloidosis, mutations in immunoglobulin light chains make the proteins unstable, allowing them to unfold in the blood and form toxic clusters (aggregates) that damage the heart. (
  • Localized forms of amyloidosis appear to be caused by local production and deposition of an amyloidogenic protein (most often immunoglobulin light chains) within the affected organ rather than by deposition of circulating proteins. (
  • The tau proteins were identified in 1975 as heat-stable proteins essential for microtubule assembly, and since then they have been characterized as intrinsically disordered proteins. (
  • Retention and accumulation of this type of amyloid protein is presumed to be the main pathogenic process underlying beta-2m amyloidosis. (
  • Taken together, these results demonstrate that curcumin is a PPARα activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner. (
  • In the recent PNAS study, the Wiseman lab, in collaboration with Jeffery Kelly's lab at TSRI, focused on a systemic amyloid disease called light chain amyloidosis, where the unstable proteins are called light chain immunoglobulins. (
  • Current treatments for light chain amyloidosis involve chemotherapy to kill the dysfunctional cells that secrete the disease-associated proteins, but about 30 percent of patients have significant buildup of light chain in the heart, making them too weak for this treatment. (
  • Although ApoA-I amyloidosis is systemic, the different amyloidogenic variants show a preferential tissue accumulation that appears to correlate with the location of the mutation in the protein sequence and with the local extracellular microenvironment. (
  • For amyloidosis to develop, in addition to production of amyloidogenic proteins, there is probably also a failure of the normal clearance mechanisms for such misfolded proteins. (
  • In systemic amyloidosis, circulating amyloidogenic proteins form deposits in a variety of organs. (
  • Although there are more than 36 types of amyloid precursor proteins, only nine build up in the myocardium and cause cardiac amyloidosis. (
  • The different types of amyloidosis are named by the letter "A" followed by an abbreviation for the type of precursor protein that has misfolded. (
  • Amyloidoses comprise a class of diseases characterized pathologically by the presence of deposits of fibrillar, aberrantly folded proteins, known as amyloids. (
  • Scientists at The Scripps Research Institute (TSRI) have discovered a way to decrease deadly protein deposits in the heart, kidney and other organs associated with a group of human diseases called the systemic amyloid diseases. (
  • In related studies published recently in the journals Proceedings of the National Academy of Sciences ( PNAS ) and Chemistry & Biology , Wiseman and his colleagues described a process that can catch unstable proteins before they are released from the cell and form deposits. (
  • these deposits are composed of aggregated, misfolded proteins that are normally cleared by the process of autophagy. (
  • More interestingly, since the rodent form of IAPP does not form amyloidogenic aggregated, misfolded cytotoxic deposits, the researchers duplicated their experiments using HUMAN islets and found that rapamycin decreased IAPP content by 31% ±12.4% as compared to untreated human islets. (
  • In addition to the fibrillar amyloid protein, the deposits also contain serum amyloid P component and glycosaminoglycans. (
  • After an increase in serum levels of the free chains, the protein deposits in organs, causing significant dysfunction . (
  • These protein deposits most frequently occur in the peripheral nervous system, which is made up of nerves that connect the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. (
  • Protein deposits in these nerves result in a loss of sensation or in muscle weakness in the extremities (peripheral neuropathy). (
  • [9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross- polarized light after staining with the dye Congo red , as well as a fibrillar ultrastructure when viewed with an electron microscope . (
  • [10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. (
  • The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT (microtubule-associated protein tau). (
  • In humans, the MAPT gene for encoding tau protein is located on chromosome 17q21, containing 16 exons. (
  • High density arrays of extraordinarily sensitive integrated microring resonators will allow many gene and protein signatures to be simultaneously quantitated from a single patient sample. (
  • For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (
  • To investigate the APP in vivo interactome in an unbiased manner, we generated mice that harbor a mouse prion protein promoter-driven cDNA encoding human APP-695 fused to a C-terminal affinity tag. (
  • Aβ is liberated from type I integral membrane proteins, termed β-amyloid precursor proteins (APPs), by the concerted action of β-secretase (BACE1) and γ-secretase (for review, see Selkoe, 2002 ). (
  • For the amyloid beta-protein (Abeta), a consensus about the size and relative abundance of small oligomers has not been achieved. (
  • Overexpression of amyloid precursor protein (APP) and amyloid-beta is modulated via the amyloidogenic pathway, which plays a crucial role in neuroinflammation. (
  • PICUP thus is a powerful tool for the investigation of small, metastable protein oligomers. (
  • The method provides essential insights into the factors that control the assembly of pathogenic protein oligomers, facilitating efforts toward the development of therapeutic agents. (
  • However, some prefibrillar oligomers of amyloidogenic proteins have direct cellular toxicity, an important component of disease pathogenesis. (
  • The authors propose that Aβ is among the proteins that enhance HSV1 infectivity. (
  • We describe here the application of the method Photoinduced Cross-Linking of Unmodified Proteins (PICUP) to the study of Abeta oligomerization. (
  • This approach distinguishes oligomerization patterns of amyloidogenic and nonamyloidogenic proteins, allows quantification of each component in oligomer mixtures, and provides a means of correlating primary structure modifications with assembly characteristics. (
  • Structural coordinates and structural factors have been deposited in the Protein Data Bank under accession numbers 3OGK , 3OGL and 3OGM . (
  • [13] [14] Because proteins share a common structural feature known as the polypeptide backbone, all proteins have the potential to misfold under some circumstances. (
  • [15] However, only a relatively small number of proteins are linked to proteopathic disorders, possibly due to structural idiosyncrasies of the vulnerable proteins. (
  • 1991), none of the the structural details of the heterogeneous protein surface and experimental studies mentioned so far could provide un- takes into account a variety of short-range interactions, direct ambiguous information about oligomer structure. (
  • Biofilm is a complex matrix made up of extracellular polysaccharides, DNA, and proteins that protect bacteria against physical, chemical, and biological stresses and allow them to survive in harsh environments. (
  • Systemic amyloid diseases are caused by the buildup of unstable protein in extracellular environments such as the blood. (
  • If we can develop a strategy to reduce the load that's coming from these proteins, then we can open up treatment options that could be broadly applied to treat multiple systemic amyloid diseases," said Luke Wiseman, assistant professor at TSRI and a senior author of the new research. (
  • Purification of APP-AT protein complexes and identification of the constituents by mass spectrometry revealed several previously reported APP-interacting proteins as well as proteins involved in synaptic maintenance. (
  • Tau is a negative regulator of mRNA translation in Drosophila, mouse, and human brains, through its binding to ribosomes, which results in impaired ribosomal function, reduction of protein synthesis and altered synaptic function. (
  • Atypical, non-standard roles of tau are also under current investigation, such as its involvement in chromosome stability, its interaction with the cellular transcriptome, its interaction with other cytoskeletal or synaptic proteins, its involvement in myelination or in brain insulin signaling, its role in the exposure to chronic stress and in depression, etc. (
  • Amyloid Precursor Protein (APP) Controls the Expression of the Transcriptional Activator Neuronal PAS Domain Protein 4 (NPAS4) and Synaptic GABA Release. (
  • Wozniak PW, Kotulska (2015) AmyLoad: website dedicated to amyloidogenic protein fragments. (
  • A buildup of proteins in this tissue can cause stroke and bleeding in the brain, an accumulation of fluid in the brain (hydrocephalus), difficulty coordinating movements (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and loss of intellectual function (dementia). (
  • proteinopathic adj ), or proteopathy , protein conformational disorder , or protein misfolding disease , is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells , tissues and organs of the body. (
  • [5] In this aggregated form, the protein is resistant to clearance and can interfere with the normal capacity of the affected organs. (
  • The accumulation of these proteins damages organs such as the heart, kidney and gut, leading to organ malfunction and, eventually, death. (
  • These proteins may accumulate locally, causing relatively few symptoms, or widely, involving multiple organs and causing severe multiorgan failure. (
  • During ischemic conditions, the activity of the anti-inflammatory non-amyloidogenic pathway decreases, thus increasing the activity of amyloidogenic pathway. (
  • The soluble alpha form of APP (sAPPα), formed via the non-amyloidogenic pathway, exhibits neuroprotective effects against neurological diseases. (
  • APP undergoes sequential proteolytic processing first by β-secretase (BACE1, aspartyl protease) and then by γ-secretase, in the amyloidogenic pathway. (
  • Autophagy, a highly regulated pathway, is entered by cells under various conditions including starvation, protein misfolding and oxidative stress. (
  • This approach identified an ER mechanism called the Unfolded Protein Response, or UPR, as a pathway whose activation preferentially reduces secretion of disease-associated light chains. (
  • Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a multifunctional RNA-binding protein that is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis and multisystem proteinopathy. (
  • Transcription of the Envelope Protein by 1-L Protein-RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis. (
  • Competitive amyloidogenic pathways play an important role in many neurological diseases such as the onset of various degenerative diseases and ischemic stroke. (
  • They assume that Aβ is recruited by HSV1 to be part of the protein corona that enhances the virus's pathogenic actions. (
  • We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. (
  • Data indicated that ApoA-I variants exerted a cytotoxic effect in a time and cell-type-specific manner that seems to be due to protein accumulation in lysosomes. (
  • Tau proteins interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. (
  • 1997) at higher how proteins interact with themselves in solution. (
  • Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission. (
  • We focused on four ApoA-I amyloidogenic variants and analyzed their cytotoxicity as well as their ability to alter redox homeostasis in cell lines from different tissues (liver, kidney, heart, skin). (
  • The AmyLoad website contains about 1400 unique amyloidogenic and non-amyloidogenic sequence entries. (
  • In the human brain, tau proteins constitute a family of six isoforms with a range of 352-441 amino acids. (
  • 1 A new paper 1 reports on how the loss of autophagy along with beta cell expression of IAPP (amyloid islet polypeptide, also called amylin), a 37 amino acid protein coexpressed and released by pancreatic beta cells along with insulin, results in the death (apoptosis) of beta cells. (
  • Tau proteins are found more often in neurons than in non-neuronal cells in humans. (
  • The addition of an affinity tag allowed us to avoid the use of antibodies targeted toward the intracellular C-terminal tail of APP, a region to which a number of reported interacting proteins bind ( King and Turner, 2004 ). (
  • In most, if not all proteinopathies, a change in the 3-dimensional folding conformation increases the tendency of a specific protein to bind to itself. (
  • They mostly belong to class G or M immunoglobulins and recognize and induce clearance of altered self-structures, including oxidatively damaged components, dying cells and aggregated or misfolded proteins [ 7 - 10 ]. (
  • γ-Secretase performs the subsequent cleavage at S3 releasing Notch intracellular domain (NICD) from the membrane and allowing for signal transduction through binding with the CBL-1, Su(H), Lag-1 family of DNA binding proteins. (
  • Today, several proteomics approaches (such as chemical, quantitative and functional proteomics, including the analyses of protein expression profiles, protein interaction networks and post-translational modifications) are widely carried out by clinicians and pharmaceutical companies. (
  • In this review, we assess the potential role of putative gut microbiota products in the etiopathogeny of Parkinson's disease, with a special emphasis on functional bacterial amyloid proteins, bacterial biosurfactants, endotoxins and short-chain fatty acids. (
  • Theoretically, the possibilities include (1) a primary T-cell mediated autoimmune response causing muscle damage, (2) a primary degenerative process involving abnormal protein processing leading to a secondary inflammatory response, and (3) separate and independent immune and degenerative processes caused by an external trigger. (
  • Wiseman, Kelly and their teams went to the source of the unstable proteins: a part of the cell called the endoplasmic reticulum (ER). (
  • Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei. (
  • Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs. (
  • The mRNA vaccines contain only the code for the SARS-CoV-2 envelope spike protein, whereas the DNA-based vaccines both contain an adenovirus viral vector that has been augmented with DNA that codes for the SARS-CoV-2 spike protein. (
  • The finding that HSV1 accumulates a protein corona is potentially an important advance in understanding viral infectivity. (
  • In addition to its microtubule-stabilizing function, Tau has also been found to recruit signaling proteins and to regulate microtubule-mediated axonal transport. (
  • It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE. (
  • We find that the fibril core is formed by a 45-residue segment of the prion-like low-complexity domain of the protein, whereas the remaining parts of the protein (275 residues) form a fuzzy coat around the fibril core. (
  • The 20 residue long Trp-cage miniprotein is a great model to complete both computational and experimental studies on protein folding and stability. (
  • Interestingly, the team reported that ATF6 activation increases the ability of the cell to "read" the stability of proteins. (
  • Tau interacts specifically with several ribosomal proteins, including the crucial regulator of translation rpS6. (