Amyloid precursor protein secretases. Medical search

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.

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.

A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.

Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.

A 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 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 subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.

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.

Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.

Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.

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.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

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 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 heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)

Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.

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 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.

Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).

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.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

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.

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.

Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.

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)

A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.

Established cell cultures that have the potential to propagate indefinitely.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

A 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.

The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.

A family of proteins that share sequence similarity with the low density lipoprotein receptor (RECEPTORS, LDL).

The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.

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 uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)

Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.

The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3)

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.

A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.

Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

A plant genus of the family CONVOLVULACEAE. The common name of morning glory also refers to IPOMOEA. The common name of bindweed also refers to IPOMOEA; CALYSTEGIA; or POLYGONUM.

Proteins prepared by recombinant DNA technology.

Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.

Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.

A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)

An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC 3.4.24.56.

Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).

A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.

In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.

An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.

Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.

An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.

Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.

Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.

Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.

Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

A cell line derived from cultured tumor cells.

The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.

The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

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.

CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)

A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.

Peptides composed of two amino acid units.

A potentially neurotoxic 8-hydroxyquinoline derivative long used as a topical anti-infective, intestinal antiamebic, and vaginal trichomonacide. The oral preparation has been shown to cause subacute myelo-optic neuropathy and has been banned worldwide.

A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.

A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.

The period of history from 1451 through 1600 of the common era.

The rate dynamics in chemical or physical systems.

Physiologically inactive substances that can be converted to active enzymes.

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.

Incorporation of biotinyl groups into molecules.

A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.

Elements of limited time intervals, contributing to particular results or situations.

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.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.

Compound used for therapy of thiamine deficiency. It has also been suggested for several non-deficiency disorders but has not yet proven useful.

Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).

A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)

Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.

A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.

A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)

Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.

Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.

Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.

Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.

Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.

Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. (1/1874)

Proteolytic processing of the amyloid precursor protein by beta-secretase yields A4CT (C99), which is cleaved further by the as yet unknown gamma-secretase, yielding the beta-amyloid (Abeta) peptide with 40 (Abeta40) or 42 residues (Abeta42). Because the position of gamma-secretase cleavage is crucial for the pathogenesis of Alzheimer's disease, we individually replaced all membrane-domain residues of A4CT outside the Abeta domain with phenylalanine, stably transfected the constructs in COS7 cells, and determined the effect of these mutations on the cleavage specificity of gamma-secretase (Abeta42/Abeta40 ratio). Compared with wild-type A4CT, mutations at Val-44, Ile-47, and Val-50 led to decreased Abeta42/Abeta40 ratios, whereas mutations at Thr-43, Ile-45, Val-46, Leu-49, and Met-51 led to increased Abeta42/Abeta40 ratios. A massive effect was observed for I45F (34-fold increase) making this construct important for the generation of animal models for Alzheimer's disease. Unlike the other mutations, A4CT-V44F was processed mainly to Abeta38, as determined by mass spectrometry. Our data provide a detailed model for the active site of gamma-secretase: gamma-secretase interacts with A4CT by binding to one side of the alpha-helical transmembrane domain of A4CT. Mutations in the transmembrane domain of A4CT interfere with the interaction between gamma-secretase and A4CT and, thus, alter the cleavage specificity of gamma-secretase. (+info)

Calpain inhibitor I increases beta-amyloid peptide production by inhibiting the degradation of the substrate of gamma-secretase. Evidence that substrate availability limits beta-amyloid peptide production. (2/1874)

The calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN) has been reported to have complex effects on the production of the beta-amyloid peptide (Abeta). In this study, the effects of ALLN on the processing of the amyloid precursor protein (APP) to Abeta were examined in 293 cells expressing APP or the C-terminal 100 amino acids of APP (C100). In cells expressing APP or low levels of C100, ALLN increased Abeta40 and Abeta42 secretion at low concentrations, decreased Abeta40 and Abeta42 secretion at high concentrations, and increased cellular levels of C100 in a concentration-dependent manner by inhibiting C100 degradation. Low concentrations of ALLN increased Abeta42 secretion more dramatically than Abeta40 secretion. ALLN treatment of cells expressing high levels of C100 did not alter cellular C100 levels and inhibited Abeta40 and Abeta42 secretion with similar IC50 values. These results suggest that C100 can be processed both by gamma-secretase and by a degradation pathway that is inhibited by low concentrations of ALLN. The data are consistent with inhibition of gamma-secretase by high concentrations of ALLN but do not support previous assertions that ALLN is a selective inhibitor of the gamma-secretase producing Abeta40. Rather, Abeta42 secretion may be more dependent on C100 substrate concentration than Abeta40 secretion. (+info)

Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. (3/1874)

Amyloid beta peptide (Abeta), the principal proteinaceous component of amyloid plaques in brains of Alzheimer's disease patients, is derived by proteolytic cleavage of the amyloid precursor protein (APP). Proteolytic cleavage of APP by a putative alpha-secretase within the Abeta sequence precludes the formation of the amyloidogenic peptides and leads to the release of soluble APPsalpha into the medium. By overexpression of a disintegrin and metalloprotease (ADAM), classified as ADAM 10, in HEK 293 cells, basal and protein kinase C-stimulated alpha-secretase activity was increased severalfold. The proteolytically activated form of ADAM 10 was localized by cell surface biotinylation in the plasma membrane, but the majority of the proenzyme was found in the Golgi. These results support the view that APP is cleaved both at the cell surface and along the secretory pathway. Endogenous alpha-secretase activity was inhibited by a dominant negative form of ADAM 10 with a point mutation in the zinc binding site. Studies with purified ADAM 10 and Abeta fragments confirm the correct alpha-secretase cleavage site and demonstrate a dependence on the substrate's conformation. Our results provide evidence that ADAM 10 has alpha-secretase activity and many properties expected for the proteolytic processing of APP. Increases of its expression and activity might be beneficial for the treatment of Alzheimer's disease. (+info)

Protein kinase C and amyloid precursor protein processing in skin fibroblasts from sporadic and familial Alzheimer's disease cases. (4/1874)

Non-amyloidogenic alpha-secretase processing of amyloid precursor protein (APP) is stimulated by protein kinase C (PKC). Levels and activity of PKC are decreased in sporadic Alzheimer's disease skin fibroblasts. We investigated whether alterations in PKC and PKC-mediated APP processing occur also in fibroblasts established from individuals with familial Alzheimer's disease APP KM670/671NL, PS1 M146V and H163Y mutations. These pathogenic mutations are known to alter APP metabolism to increase Abeta. PKC activities, but not levels, were decreased by 50% in soluble fractions from sporadic Alzheimer's disease cases. In contrast, familial Alzheimer's disease fibroblasts showed no significant changes in PKC enzyme activity. Fibroblasts bearing the APP KM670/671NL mutation showed no significant differences in either PKC levels or PKC-mediated soluble APP (APPs) secretion, compared to controls. Fibroblasts bearing PS1 M146V and H163Y mutations showed a 30% increase in soluble PKC levels and a 40% decrease in PKC-mediated APPs secretion. These results indicate that PKC deficits are unlikely to contribute to increased Abeta seen with APP and PS1 mutations, and also that PS1 mutations decrease alpha-secretase derived APPs production independently of altered PKC activity. (+info)

Effect of protein kinase A inhibitors on the production of Abeta40 and Abeta42 by human cells expressing normal and Alzheimer's disease-linked mutated betaAPP and presenilin 1. (5/1874)

1. We previously established that the formation of both alpha- and beta/gamma-secretase-derived products generated by human embryonic kidney 293 cells (HEK293) expressing either wild type or mutant betaAPP could be stimulated by agonists of the cyclic AMP/protein kinase A pathways. This cyclic AMP-dependent effect modulates post-translational events since it is not prevented by actinomycin D or cycloheximide. 2. We show here that two protein kinase A inhibitors, H89 and PKI, both trigger dose-dependent inhibition of the basal constitutive production of Abeta40 and Abeta42 by HEK293 cells expressing wild type betaAPP751. 3. H89 also potently inhibits the total Abeta produced by the neocortical neuronal cell line TSM1. 4. These two inhibitors also drastically reduce the recovery of Abeta40 and Abeta42 produced by HEK293 cells expressing the Swedish (Sw) betaAPP and M146V-presenilin 1 (PS1) mutations responsible for cases of the early-onset forms of Familial Alzheimer's disease (FAD). 5. By contrast, H89 and PKI do not significantly affect the recovery of the physiological alpha-secretase-derived fragment APPalpha. 6. Our study indicates that protein kinase A inhibitors selectively lower the formation of Abeta40 and Abeta42 in human cells expressing normal and mutant betaAPP and PS1 without affecting the physiological alpha-secretase pathway in these cells. Selective inhibitors of protein kinase A may be of therapeutic value in both sporadic and Familial Alzheimer's disease, since they may decrease the production of Abeta that is thought to be responsible for the neurodegenerative process. (+info)

gamma-Secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid beta peptides of varying length. (6/1874)

gamma-Secretase activity is the final cleavage event that releases the amyloid beta peptide (Abeta) from the beta-secretase cleaved carboxyl-terminal fragment of the amyloid beta protein precursor (APP). No protease responsible for this highly unusual, purportedly intramembranous, cleavage has been definitively identified. We examined the substrate specificity of gamma-secretase by mutating various residues within or adjacent to the transmembrane domain of the APP and then analyzing Abeta production from cells transfected with these mutant APPs by enzyme-linked immunosorbent assay and mass spectrometry. Abeta production was also analyzed from a subset of transmembrane domain APP mutants that showed dramatic shifts in gamma-secretase cleavage in the presence or absence of pepstatin, an inhibitor of gamma-secretase activity. These studies demonstrate that gamma-secretase's cleavage specificity is primarily determined by location of the gamma-secretase cleavage site of APP with respect to the membrane, and that gamma-secretase activity is due to the action of multiple proteases exhibiting both a pepstatin- sensitive activity and a pepstatin-insensitive activity. Given that gamma-secretase is a major therapeutic target in Alzheimer's disease these studies provide important information with respect to the mechanism of Abeta production that will direct efforts to isolate the gamma-secretases and potentially to develop effective therapeutic inhibitors of pathologically relevant gamma-secretase activities. (+info)

Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. (7/1874)

The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury. Caspase-3 is the predominant caspase involved in APP cleavage, consistent with its marked elevation in dying neurons of Alzheimer's disease brains and colocalization of its APP cleavage product with A beta in senile plaques. Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease. (+info)

Thimet oligopeptidase cleaves the full-length Alzheimer amyloid precursor protein at a beta-secretase cleavage site in COS cells. (8/1874)

We developed an assay method using a novel quenched fluorescent substrate (QFS) flanking the beta-cleavage site of amyloid precursor protein (APP), and purified a candidate beta-secretase from bovine brain. N-terminal amino acid analysis showed the candidate to be thimet oligopeptidase (TOP). The cDNA for human TOP was cloned from a human brain cDNA library and expressed in COS cells. The enzyme was further purified on a Ni2+-agarose column. TOP cleaved the Swedish Alzheimer's substrate (SEVNLDAEFR) as well as the normal substrate (SEVKMDAEFR). We then coexpressed TOP with APP695 in COS cells, collected transfected cells and conditioned media, and analyzed them by immunoblotting. The antibody against the specific secreted APP cleaved by beta-secretase (sAPPbeta) detected the secretion of sAPPbeta only from APP/hTOP-overexpressing cells, and not from cells overexpressing of antisense hTOP cDNA. Finally, we analyzed the immunolocalization of overexpressed hTOP in COS cells. Most hTOP was localized in the nuclei, but a small amount was localized in the Golgi or other organelles around the nuclei. These results suggest that TOP has a beta-secretase-like activity responsible for the processing of APP. (+info)

The symptoms of Alzheimer's disease can vary from person to person and may progress slowly over time. Early symptoms may include memory loss, confusion, and difficulty with problem-solving. As the disease progresses, individuals may experience language difficulties, visual hallucinations, and changes in mood and behavior.

There is currently no cure for Alzheimer's disease, but there are several medications and therapies that can help manage its symptoms and slow its progression. These include cholinesterase inhibitors, memantine, and non-pharmacological interventions such as cognitive training and behavioral therapy.

Alzheimer's disease is a significant public health concern, affecting an estimated 5.8 million Americans in 2020. It is the sixth leading cause of death in the United States, and its prevalence is expected to continue to increase as the population ages.

There is ongoing research into the causes and potential treatments for Alzheimer's disease, including studies into the role of inflammation, oxidative stress, and the immune system. Other areas of research include the development of biomarkers for early detection and the use of advanced imaging techniques to monitor progression of the disease.

Overall, Alzheimer's disease is a complex and multifactorial disorder that poses significant challenges for individuals, families, and healthcare systems. However, with ongoing research and advances in medical technology, there is hope for improving diagnosis and treatment options in the future.

The term "amyloid" refers specifically to the type of protein aggregate that forms these plaques, and is derived from the Greek word for "flour-like." Amyloidosis is the general term used to describe the condition of having amyloid deposits in the body, while Alzheimer's disease is a specific type of amyloidosis that is characterized by the accumulation of beta-amyloid peptides in the brain.

Plaques, amyloid play a central role in the pathogenesis of many neurodegenerative diseases, and understanding their formation and clearance is an area of ongoing research. In addition to their role in Alzheimer's disease, amyloid plaques have been implicated in other conditions such as cerebral amyloid angiopathy, primary lateral sclerosis, and progressive supranuclear palsy.

Plaques, amyloid are composed of a variety of proteins, including beta-amyloid peptides, tau protein, and apolipoprotein E (apoE). The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often associated with inflammation and oxidative stress.

In addition to their role in neurodegeneration, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease. The accumulation of amyloid fibrils in these tissues can contribute to the development of insulin resistance and atherosclerosis, respectively.

Overall, plaques, amyloid are a complex and multifaceted area of research, with many open questions remaining about their formation, function, and clinical implications. Ongoing studies in this field may provide valuable insights into the pathogenesis of various diseases and ultimately lead to the development of novel therapeutic strategies for these conditions.

In conclusion, plaques, amyloid are a hallmark of several neurodegenerative diseases, including Alzheimer's disease, and have been associated with inflammation, oxidative stress, and neurodegeneration. The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often linked to the progression of the condition. Furthermore, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease, highlighting their potential clinical significance beyond neurodegeneration. Ongoing research into the mechanisms of amyloid plaque formation and clearance may lead to the development of novel therapeutic strategies for these conditions.

There are several types of amyloidosis, each with different causes and symptoms. The most common types include:

1. Primary amyloidosis: This type is caused by the production of abnormal proteins in the bone marrow. It mainly affects older adults and can lead to symptoms such as fatigue, weight loss, and numbness or tingling in the hands and feet.
2. Secondary amyloidosis: This type is caused by other conditions, such as rheumatoid arthritis, tuberculosis, or inflammatory bowel disease. It can also be caused by long-term use of certain medications, such as antibiotics or chemotherapy.
3. Familial amyloid polyneuropathy: This type is inherited and affects the nerves in the body, leading to symptoms such as muscle weakness, numbness, and pain.
4. Localized amyloidosis: This type affects a specific area of the body, such as the tongue or the skin.

The symptoms of amyloidosis can vary depending on the organs affected and the severity of the condition. Some common symptoms include:

1. Fatigue
2. Weakness
3. Pain
4. Numbness or tingling in the hands and feet
5. Swelling in the legs, ankles, and feet
6. Difficulty with speech or swallowing
7. Seizures
8. Heart problems
9. Kidney failure
10. Liver failure

The diagnosis of amyloidosis is based on a combination of physical examination, medical history, laboratory tests, and imaging studies. Laboratory tests may include blood tests to measure the levels of certain proteins in the body, as well as biopsies to examine tissue samples under a microscope. Imaging studies, such as X-rays, CT scans, and MRI scans, may be used to evaluate the organs affected by the condition.

There is no cure for amyloidosis, but treatment can help manage the symptoms and slow the progression of the disease. Treatment options may include:

1. Medications to control symptoms such as pain, swelling, and heart problems
2. Chemotherapy to reduce the production of abnormal proteins
3. Autologous stem cell transplantation to replace damaged cells with healthy ones
4. Dialysis to remove excess fluids and waste products from the body
5. Nutritional support to ensure adequate nutrition and hydration
6. Physical therapy to maintain muscle strength and mobility
7. Supportive care to manage pain, improve quality of life, and reduce stress on the family.

In conclusion, amyloidosis is a complex and rare group of diseases that can affect multiple organs and systems in the body. Early diagnosis and treatment are essential to managing the symptoms and slowing the progression of the disease. It is important for patients with suspected amyloidosis to seek medical attention from a specialist, such as a hematologist or nephrologist, for proper evaluation and treatment.

The term "cerebral" refers to the brain, "amyloid" refers to the abnormal protein deposits, and "angiopathy" refers to the damage caused to the blood vessels. CAA is often associated with other conditions such as Alzheimer's disease, Down syndrome, and other forms of dementia.

CAA is a type of small vessel ischemic disease (SVID), which affects the smaller blood vessels in the brain. The exact cause of CAA is not yet fully understood, but it is thought to be related to a combination of genetic and environmental factors. There is currently no cure for CAA, but researchers are working to develop new treatments to slow its progression and manage its symptoms.

Some common symptoms of CAA include:

* Cognitive decline
* Seizures
* Stroke-like episodes
* Memory loss
* Confusion
* Difficulty with coordination and balance

If you suspect you or a loved one may be experiencing symptoms of CAA, it is important to speak with a healthcare professional for proper diagnosis and treatment. A thorough medical history and physical examination, along with imaging tests such as MRI or CT scans, can help confirm the presence of CAA.

While there is no cure for CAA, there are several treatment options available to manage its symptoms and slow its progression. These may include medications to control seizures, improve cognitive function, and reduce inflammation. In some cases, surgery or endovascular procedures may be necessary to repair or remove damaged blood vessels.

It is important to note that CAA is a complex condition, and its management requires a multidisciplinary approach involving neurologists, geriatricians, radiologists, and other healthcare professionals. With proper diagnosis and treatment, however, many individuals with CAA are able to lead active and fulfilling lives.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Amyloidosis can affect many different parts of the body, including the nervous system, the heart, the kidneys, the liver, and other organs. In the nervous system, amyloid accumulation can lead to various neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and others.

Amyloid deposits in the nervous system can cause a range of symptoms including cognitive decline, memory loss, confusion, language impairment, and difficulty with coordination and movement. In addition, amyloid accumulation can lead to inflammation, oxidative stress, and excitotoxicity, which can further exacerbate neurodegeneration.

There are several types of amyloidosis that can affect the nervous system, including:

1. Alzheimer's disease: This is a progressive neurodegenerative disorder that is characterized by the accumulation of beta-amyloid peptides in the brain, leading to cognitive decline and memory loss.
2. Parkinson's disease: This is a neurodegenerative disorder that affects movement, balance, and coordination. It is characterized by the accumulation of alpha-synuclein protein in the brain.
3. Prion diseases: These are a group of rare, progressive neurodegenerative disorders that are caused by misfolded prion proteins. They can affect both the central and peripheral nervous systems.
4. Other forms of amyloidosis: There are several other forms of amyloidosis that can affect the nervous system, including primary lateral sclerosis, progressive supranuclear palsy, and corticobasal degeneration.

Amyloidosis can be diagnosed through a combination of clinical evaluation, imaging studies, and biopsy. Treatment options for amyloidosis vary depending on the underlying cause and severity of the disease. Some common treatments include:

1. Medications: There are several medications that can be used to treat amyloidosis, including cholinesterase inhibitors, dopamine agonists, and memantine.
2. Physical therapy: Physical therapy can help improve mobility, balance, and coordination in people with amyloidosis.
3. Speech therapy: Speech therapy can help improve communication and swallowing difficulties in people with amyloidosis.
4. Occupational therapy: Occupational therapy can help people with amyloidosis adapt to changes in their daily living activities and maintain their independence.
5. Surgery: In some cases, surgery may be necessary to relieve pressure on the brain or spinal cord caused by amyloid accumulation.

Currently, there is no cure for amyloidosis, but early diagnosis and treatment can help manage symptoms and improve quality of life. Research into new treatments and therapies is ongoing, including clinical trials exploring the use of stem cells, gene therapy, and immunotherapy to treat amyloidosis.

There are many different types of nerve degeneration that can occur in various parts of the body, including:

1. Alzheimer's disease: A progressive neurological disorder that affects memory and cognitive function, leading to degeneration of brain cells.
2. Parkinson's disease: A neurodegenerative disorder that affects movement and balance, caused by the loss of dopamine-producing neurons in the brain.
3. Amyotrophic lateral sclerosis (ALS): A progressive neurological disease that affects nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and eventually death.
4. Multiple sclerosis: An autoimmune disease that affects the central nervous system, causing inflammation and damage to nerve fibers.
5. Diabetic neuropathy: A complication of diabetes that can cause damage to nerves in the hands and feet, leading to pain, numbness, and weakness.
6. Guillain-Barré syndrome: An autoimmune disorder that can cause inflammation and damage to nerve fibers, leading to muscle weakness and paralysis.
7. Chronic inflammatory demyelinating polyneuropathy (CIDP): An autoimmune disorder that can cause inflammation and damage to nerve fibers, leading to muscle weakness and numbness.

The causes of nerve degeneration are not always known or fully understood, but some possible causes include:

1. Genetics: Some types of nerve degeneration may be inherited from one's parents.
2. Aging: As we age, our nerve cells can become damaged or degenerate, leading to a decline in cognitive and physical function.
3. Injury or trauma: Physical injury or trauma to the nervous system can cause nerve damage and degeneration.
4. Infections: Certain infections, such as viral or bacterial infections, can cause nerve damage and degeneration.
5. Autoimmune disorders: Conditions such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP) are caused by the immune system attacking and damaging nerve cells.
6. Toxins: Exposure to certain toxins, such as heavy metals or pesticides, can damage and degenerate nerve cells.
7. Poor nutrition: A diet that is deficient in essential nutrients, such as vitamin B12 or other B vitamins, can lead to nerve damage and degeneration.
8. Alcoholism: Long-term alcohol abuse can cause nerve damage and degeneration due to the toxic effects of alcohol on nerve cells.
9. Drug use: Certain drugs, such as chemotherapy drugs and antiviral medications, can damage and degenerate nerve cells.
10. Aging: As we age, our nerve cells can deteriorate and become less functional, leading to a range of cognitive and motor symptoms.

It's important to note that in some cases, nerve damage and degeneration may be irreversible, but there are often strategies that can help manage symptoms and improve quality of life. If you suspect you have nerve damage or degeneration, it's important to seek medical attention as soon as possible to receive an accurate diagnosis and appropriate treatment.

Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.

There are several different types of neuroblastoma, including:

1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.

Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:

* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate

Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.

Some common types of memory disorders include:

1. Amnesia: A condition where an individual experiences memory loss, either partial or total, due to brain damage or other causes.
2. Dementia: A broad term that describes a decline in cognitive function, including memory loss, confusion, and difficulty with communication and daily activities. Alzheimer's disease is the most common cause of dementia.
3. Mild Cognitive Impairment (MCI): A condition characterized by memory loss and other cognitive symptoms that are more severe than normal age-related changes but not as severe as dementia.
4. Attention Deficit Hyperactivity Disorder (ADHD): A neurodevelopmental disorder that affects attention, impulse control, and hyperactivity. Memory problems are often a component of ADHD.
5. Traumatic Brain Injury (TBI): A condition that occurs when the brain is injured due to a blow or jolt to the head, which can result in memory loss and other cognitive problems.
6. Stroke: A condition where blood flow to the brain is interrupted, leading to brain cell death and potential memory loss.
7. Meningitis: An inflammatory condition that affects the membranes covering the brain and spinal cord, which can lead to memory loss and other cognitive problems.
8. Encephalitis: An inflammatory condition that affects the brain directly, leading to memory loss and other cognitive problems.
9. Chronic Fatigue Syndrome (CFS): A condition characterized by persistent fatigue, memory loss, and other cognitive symptoms.
10. Sleep Disorders: Sleep disturbances can affect memory and cognitive function, including conditions such as insomnia, sleep apnea, and restless leg syndrome.

The diagnosis of memory disorders typically involves a combination of medical history, physical examination, laboratory tests, and neuropsychological evaluations. The specific treatment approach will depend on the underlying cause of the memory loss, but may include medication, behavioral interventions, and lifestyle changes.

Gliosis is made up of glial cells, which are non-neuronal cells that provide support and protection to neurons. When neural tissue is damaged, glial cells proliferate and form a scar-like tissue to fill in the gap and repair the damage. This scar tissue can be made up of astrocytes, oligodendrocytes, or microglia, depending on the type of injury and the location of the damage.

Gliosis can have both beneficial and harmful effects on the brain. On one hand, it can help to prevent further damage by providing a physical barrier against invading substances and protecting the surrounding neural tissue. It can also promote healing by bringing in immune cells and growth factors that aid in the repair process.

On the other hand, gliosis can also have negative effects on brain function. The scar tissue can disrupt normal communication between neurons, leading to impaired cognitive and motor function. In addition, if the scar tissue is too extensive or severe, it can compress or displaces surrounding neural tissue, leading to long-term neurological deficits or even death.

There are several ways to diagnose gliosis, including magnetic resonance imaging (MRI), positron emission tomography (PET), and histopathology. Treatment options for gliosis depend on the underlying cause of the condition and can include medications, surgery, or a combination of both.

In summary, gliosis is a type of scar tissue that forms in the brain and spinal cord as a result of damage to neural tissue. It can have both beneficial and harmful effects on brain function, and diagnosis and treatment options vary depending on the underlying cause of the condition.

Some common examples of neurodegenerative diseases include:

1. Alzheimer's disease: A progressive loss of cognitive function, memory, and thinking skills that is the most common form of dementia.
2. Parkinson's disease: A disorder that affects movement, balance, and coordination, causing tremors, rigidity, and difficulty with walking.
3. Huntington's disease: An inherited condition that causes progressive loss of cognitive, motor, and psychiatric functions.
4. Amyotrophic lateral sclerosis (ALS): A disease that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness, paralysis, and eventually death.
5. Prion diseases: A group of rare and fatal disorders caused by misfolded proteins in the brain, leading to neurodegeneration and death.
6. Creutzfeldt-Jakob disease: A rare, degenerative, and fatal brain disorder caused by an abnormal form of a protein called a prion.
7. Frontotemporal dementia: A group of diseases that affect the front and temporal lobes of the brain, leading to changes in personality, behavior, and language.

Neurodegenerative diseases can be caused by a variety of factors, including genetics, age, lifestyle, and environmental factors. They are typically diagnosed through a combination of medical history, physical examination, laboratory tests, and imaging studies. Treatment options for neurodegenerative diseases vary depending on the specific condition and its underlying causes, but may include medications, therapy, and lifestyle changes.

Preventing or slowing the progression of neurodegenerative diseases is a major focus of current research, with various potential therapeutic strategies being explored, such as:

1. Stem cell therapies: Using stem cells to replace damaged neurons and restore brain function.
2. Gene therapies: Replacing or editing genes that are linked to neurodegenerative diseases.
3. Small molecule therapies: Developing small molecules that can slow or prevent the progression of neurodegenerative diseases.
4. Immunotherapies: Harnessing the immune system to combat neurodegenerative diseases.
5. Lifestyle interventions: Promoting healthy lifestyle choices, such as regular exercise and a balanced diet, to reduce the risk of developing neurodegenerative diseases.

In conclusion, neurodegenerative diseases are a complex and diverse group of disorders that can have a profound impact on individuals and society. While there is currently no cure for these conditions, research is providing new insights into their causes and potential treatments. By continuing to invest in research and developing innovative therapeutic strategies, we can work towards improving the lives of those affected by neurodegenerative diseases and ultimately finding a cure.

Down syndrome can be diagnosed before birth through prenatal testing, such as chorionic villus sampling or amniocentesis, or after birth through a blood test. The symptoms of Down syndrome can vary from person to person, but common physical features include:

* A flat face with a short neck and small ears
* A short stature
* A wide, short hands with short fingers
* A small head
* Almond-shaped eyes that are slanted upward
* A single crease in the palm of the hand

People with Down syndrome may also have cognitive delays and intellectual disability, as well as increased risk of certain medical conditions such as heart defects, gastrointestinal problems, and hearing and vision loss.

There is no cure for Down syndrome, but early intervention and proper medical care can greatly improve the quality of life for individuals with the condition. Treatment may include speech and language therapy, occupational therapy, physical therapy, and special education programs. With appropriate support and resources, people with Down syndrome can lead fulfilling and productive lives.

Among other roles in the cell, secretases act on the amyloid-beta precursor protein (APP) to cleave the protein into three ... Secretases are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane. ... BACE is a transmembrane protein with an extracellular aspartic acid protease domain. γ-secretase is actually a protein complex ... no amyloid beta is formed because α-secretase recognizes a target protein sequence closer to the cell surface than BACE. The ...

https://en.wikipedia.org/wiki/Amyloid-beta_precursor_protein_secretase

... and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). Aβ circulates in plasma, ... Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ... December 2014). "Amyloid-β precursor protein promotes cell proliferation and motility of advanced breast cancer". BMC Cancer. ... The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield A ...

https://en.wikipedia.org/wiki/Amyloid_beta

Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. ... "Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the ... De Strooper, B; Annaert, W (2000). "Proteolytic processing and cell biological functions of the amyloid precursor protein". J ... "The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein". FASEB J. ...

https://en.wikipedia.org/wiki/Alpha_secretase

His research interest are the secretases, proteases which cleave the amyloid precursor protein (APP), resulting in amyloid ... "Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein". Nature. 391 (6665): 387-90. doi:10.1038/ ... The amyloid peptide is the main constituent of the plaques in the brain of people with Alzheimer's disease. Together with ...

https://en.wikipedia.org/wiki/Bart_De_Strooper

The best-characterized gamma-secretase substrates are the Notch receptor and amyloid precursor protein (APP). Presenilins' role ... protein. To form Aβ, APP must be cut by two enzymes, beta secretases and gamma secretase. Presenilin is the sub-component of ... or the amyloid precursor protein (APP) can be found. The majority of these cases carry mutant presenilin genes. An important ... January 1997). "Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both ...

https://en.wikipedia.org/wiki/Presenilin

Aβ42 is generated by the enzymatic cleavage of the β-amyloid precursor protein (βΑPP) through β- and γ- secretases. Like other ... while up-regulating the α-secretase ADAM10 and the secreted amyloid precursor protein-α (sAPPα). Overall, the above mechanism ... Specifically, PD1 regulates this protein family by promoting the dephosphorylation of Bcl-xL by protein phosphatase 2A (PP2A) ... the release of Aβ42 down-regulates the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulates the pro-apoptotic proteins Bax ...

https://en.wikipedia.org/wiki/Protectin_D1

The amyloid precursor protein (APP) is consecutively transported from the ER after its synthesis to the plasma membrane via the ... The amyloidogenic pathway leads to APP processing by γ-secretases and β-secretases such as BACE1, resulting in production of ... are involved in protein-protein interactions. The SNX8 protein, even though is very similar to the other sorting nexins, ... SNX8 protein regulates cholesterol levels as an activator of the SREBPs (Sterol Regulatory Element Binding Proteins), which is ...

https://en.wikipedia.org/wiki/SNX8

... protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor ... Li Q, Südhof TC (2004). "Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1". J. Biol ... 1998). "Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 ... precursor-like protein 1". Wasco W, Brook JD, Tanzi RE (January 1993). "The amyloid precursor-like protein (APLP) gene maps to ...

https://en.wikipedia.org/wiki/APLP1

... amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo". Proceedings of the National Academy ... by proteases referred to as the β and γ secretases. The physiological role of this processing is unclear, though it may play a ... Aβ is a byproduct generated as the result of proteolytic processing of the amyloid precursor protein (APP) ... Kerr ML, Small DH (April 2005). "Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: function, ...

https://en.wikipedia.org/wiki/Insulin-degrading_enzyme

... generates from the 17-40 or 17-42 sequence of the amyloid precursor protein (APP), which is a type I integral ... Under normal physiological conditions, APP is processed with three different proteolytic enzymes: α-, β- and γ-secretases. At ... and γ-secretase cleavage from the amyloid precursor protein (APP). It is known to be the major constituent of diffuse plaques ... Integral membrane proteins, Human proteins, Enzymes, Alzheimer's disease, Down syndrome). ...

https://en.wikipedia.org/wiki/P3_peptide

... and β-amyloid precursor protein secretases and therefore inhibits formation of the beta amyloid peptide that forms amyloid ... however it has been demonstrated that expression of TMEM59 protein inhibits Golgi glycosylation of amyloid precursor protein ( ... Transmembrane protein 59 is a protein that in humans is encoded by the TMEM59 gene. TMEM59 is a membrane bound protein that is ... and secretion of the amyloid precursor protein". The Journal of Biological Chemistry. 285 (27): 20664-74. doi:10.1074/jbc. ...

https://en.wikipedia.org/wiki/TMEM59

The amyloid-β precursor protein (AβPP), and all associated secretases, are expressed early in development and play a key role ... 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 ... Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause ...

https://en.wikipedia.org/wiki/Amyloid-beta_precursor_protein

Selkoe, DJ (1999). "Chapter 19: Biology of β-amyloid precursor protein and the mechanism of Alzheimer disease". In Terry, RD; ... The sequential actions of these secretases results in Aβ protein fragments that are released into the extracellular space The ... Amyloid beta (Aβ) is a small protein, most often 40 or 42 amino acids in length, that is released from a longer parent protein ... Suh YH; Checler F (September 2002). "Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and ...

https://en.wikipedia.org/wiki/Amyloid_plaques

Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor ... A delicate balance of the enzymes secretases regulate the amyloid-beta accumulation. Alpha Secretase can render a non- ... March 2006). "The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production". Nature. ... is a short peptide that is a proteolytic byproduct of the transmembrane protein amyloid precursor protein (APP), whose function ...

https://en.wikipedia.org/wiki/Biochemistry_of_Alzheimer's_disease

... γ-secretase are primary proteolytic enzymes responsible for the generation of pathogenic amyloid β-peptides (Aβ) in Alzheimers ... The molecular link between beta- and gamma-secretase activity on the amyloid beta precursor protein. Tabaton M, Tamagno E. ... Modeling protein-protein interactions in axon initial segment to understand their potential impact on action potential ... Alzheimers secretases regulate voltage-gated sodium channels Dora M Kovacs 1 , Manuel T Gersbacher, Doo Yeon Kim ...

https://pubmed.ncbi.nlm.nih.gov/20817076/

Because β-amyloid peptide (Aβ) is the pathological hallmark of AD, the aim of this study is to verify whether 27-OHC could lead ... Amyloid Precursor Protein Secretases Actions. * Search in PubMed * Search in MeSH * Add to Search ... BACE1 protein, H. ADAM10 protein, I. LRP1 protein, J. RAGE protein, K. IDE mRNA, L. NEP mRNA, M. IDE protein, N. NEP protein. ... Gene and protein expressions of factors related to Aβ metabolism. A. APP mRNA, B. BACE1 mRNA, C. ADAM10 mRNA, D. LRP1 mRNA, E. ...

http://www.ncbi.nlm.nih.gov/pubmed/30582229

Amyloid Precursor Protein Secretases / genetics Actions. * Search in PubMed * Search in MeSH ... Familial Alzheimers disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor ... Amyloid precursor protein processing in human neurons with an allelic series of the PSEN1 intron 4 deletion mutation and total ... Anthony T.E., Mason H.A., Gridley T., Fishell G., Heintz N. Brain lipid-binding protein is a direct target of Notch signaling ...

https://pubmed.ncbi.nlm.nih.gov/33440141/

MeSH Terms: Amyloid Precursor Protein Secretases/metabolism; Arsenites/pharmacology*; Calcium-Binding Proteins/metabolism; Cell ... Jagged-1 Protein; Keratinocytes/metabolism*; Membrane Proteins/metabolism; Models, Biological; Protein Binding; Quinazolines; ... Receptor, Notch1/metabolism*; Receptors, Notch/metabolism; Serrate-Jagged Proteins; Signal Transduction; Skin Neoplasms/ ...

https://tools.niehs.nih.gov/portfolio/index.cfm?do=portfolio.publicationDetail&id=1322460

Targeting amyloid precursor protein secretases: Alzheimers disease and beyond.. Ganjei JK. Drug News Perspect; 2010 Nov; 23(9 ... 3. Alzheimers therapeutics: continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond? ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=19127484&mod=related&page=1&outid=&proj=

Amyloid Precursor Protein Secretases Preferred Term Term UI T670714. Date04/05/2006. LexicalTag NON. ThesaurusID NLM (2007). ... Amyloid Precursor Protein Secretases Preferred Concept UI. M0205216. Registry Number. EC 3.4.-. Related Numbers. EC 3.4.-. ... Amyloid Precursor Protein Secretase Secretase Secretases alpha-Secretase beta-Secretase gamma-Secretase Registry Number. EC 3.4 ... Amyloid Precursor Protein Secretases. Tree Number(s). D08.811.277.656.300.032. Unique ID. D053829. RDF Unique Identifier. http ...

https://meshb.nlm.nih.gov/record/ui?ui=D053829

... exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is ... Amyloid Beta: The Foremost Protagonist in Alzheimers Disease: 10.4018/978-1-7998-3441-0.ch001: Alzheimers disease (AD), ... Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha ... beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in ...

https://www.igi-global.com/chapter/amyloid-beta/261623

17-40 Beta-Amyloid peptides. Pyroglutamate-modified (Pyr) beta-Amyloid 3-40 and 11-40 have been described as major compounds in ... Sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by secretases (α, β, γ) generates beta-Amyloid peptide ... Beta-Amyloid 1-42 forms a major component of amyloid plaques in neurons of Alzheimers disease (AD) brains, while beta-Amyloid ... Beta-Amyloid x-42. A large collection of Beta-Amyloid X-42 fragments from 2 to 23-42 ...

https://www.anaspec.com/en/beta-amyloid-x-40-peptides

Amyloid Precursor Protein Secretases Entry term(s). APP Secretase Amyloid Precursor Protein Secretase Secretase Secretase, APP ... Amyloid precursor protein secretases Entry term(s):. APP Secretase. Amyloid Precursor Protein Secretase. Secretase. Secretase, ... Amyloid Precursor Protein Secretases - Preferred Concept UI. M0205216. Scope note. Endopeptidases that are specific for AMYLOID ... Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma ...

https://decs.bvsalud.org/en/ths/resource/?id=52219&filter=ths_exact_term&q=SECRETASES+DA+PROTE%C3%8DNA+PRECURSORA+DO+AMILOIDE

Aβ peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by β-secretases ... and γ-secretases generating diverse Aβ species. Aβ ... Amyloid precursor protein is a 770 amino acid protein with a ... beta-amyloid peptide, alzheimer disease amyloid protein, cerebral vascular amyloid peptide, APP, Amyloid Precursor Protein ... Aβ peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by β-secretases ...

https://www.biolegend.com/fr-lu/products/alexa-fluor-647-anti-beta-amyloid-1-16-antibody-1-16-16576?GroupID=BLG15648

https://meshb-prev.nlm.nih.gov/record/ui?ui=D053829

Amyloid Precursor Protein Secretases 100% * Cerebrospinal Fluid 70% * Alzheimer Disease 62% * Amyloid beta-Protein Precursor 56 ... Neuronal clearance of amyloid-β by endocytic receptor LRP1. Kanekiyo, T., Cirrito, J. R., Liu, C. C., Shinohara, M., Li, J., ... Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Roe, C. M., Fagan, A. M., Grant, E ... Amyloid-beta oligomerization in Alzheimer dementia versus high-pathology controls. Esparza, T. J., Zhao, H., Cirrito, J. R., ...

https://profiles.wustl.edu/en/organisations/center-for-brain-immunology-glia-big/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle&ordering=publicationYearThenTitle&descending=false&page=10

... amyloid precursor protein) under the action of certain enzymes (secretases). His work and that of other scientists ultimately ... At the beginning of the 1990s Haass started working on a small protein called "amyloid beta-peptide". This molecule aggregates ... the TREM2 protein) triggers microglia to remove deposits of amyloid, particularly in the early stages of disease. Haass then ... Contrary to what was thought at the time, Haass was able to prove that amyloid is not necessarily a component of pathological ...

https://www.dzne.de/en/news/prizes-and-awards/news/award-for-munich-alzheimers-researcher/

Secretases da Proteína Precursora do Amiloide; Precursor de Proteína beta-Amiloide; Secretases da Proteína Precursora do ... of amyloid precursor protein (APP) into pathologically relevant amyloid-ß peptides (Aßs). The detailed mechanisms of the unique ... A thermodynamic investigation of amyloid precursor protein processing by human Î³-secretas ... A thermodynamic investigation of amyloid precursor protein processing by human Î³-secretase. ...

https://pesquisa.bvsalud.org/portal/resource/pt/mdl-35982231

A ProteinAmyloid beta-Protein PrecursorIslet Amyloid PolypeptideSerum Amyloid P-ComponentAmyloid Precursor Protein Secretases ... Amyloid beta-Protein Precursor. A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to ... Amyloid Precursor Protein Secretases. Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes ... NeuropathiesAmyloid beta-PeptidesSerum Amyloid A ProteinPeripheral Nervous System DiseasesAmyloid beta-Protein PrecursorPlaque ...

https://lookformedical.com/en/search/amyloid-neuropathies

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 94% * Amyloid Precursor Protein Secretases 58% ...

https://einstein.elsevierpure.com/en/publications/an-activating-intragenic-deletion-in-notch1-in-human-t-all-2/fingerprints/

Amyloid Precursor Protein Secretases 100% * Innate Immunity 74% * Interferons 74% * Alzheimer Disease 62% ... The innate immunity protein IFITM3 modulates γ-secretase in Alzheimers disease. Hur, J. Y., Frost, G. R., Wu, X., Crump, C., ... Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques ... The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimers disease. ...

https://scholars.mssm.edu/en/persons/alison-goate/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Farticle&page=1

Amyloid Precursor Protein Secretases Medicine & Life Sciences 100% * Amino Acyl-tRNA Synthetases Medicine & Life Sciences 57% ... Brain metabolism in tau and amyloid mouse models of Alzheimers disease: An MRI study. Wei, Z., Xu, J., Chen, L., Hirschler, L. ... Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes. Kim, D. W., Tu ...

https://pure.johnshopkins.edu/en/persons/tong-li

Amyloid Precursor Protein Secretases 5% * Thermogenesis 5% * Brown Adipose Tissue 5% * White Adipose Tissue 5% ...

https://portal.findresearcher.sdu.dk/da/persons/meshailokla/fingerprints/

... such as the beta-amyloid precursor protein (APP) and presenilins (PS1, PS2). These proteins along with tau, secretases, such as ... such as the beta-amyloid precursor protein (APP), presenilins (PS1, PS2), secretases, such as β-amyloid cleaving enzyme (BACE ... The term "β-amyloid precursor protein" or "APP" as used herein is defined as a polypeptide that is encoded by a gene of the ... for decreasing the level of at least one amyloid peptide produced by a mammalian cell that expresses amyloid precursor protein ...

https://patents.justia.com/patent/20050113458

Amyloid Precursor Protein Secretases Medicine & Life Sciences 28% View full fingerprint Cite this. * APA ...

https://augusta.elsevierpure.com/en/publications/notch-reporter-activity-in-breast-cancer-cell-lines-identifies-a-

Amyloid Precursor Protein Secretases Medicine & Life Sciences 100% * Amyloid Medicine & Life Sciences 76% ... PEN-2 is a component of the γ-secretase complex, which is involved in the cleavage of the β-amyloid precursor protein. The aim ... N2 - PEN-2 is a component of the γ-secretase complex, which is involved in the cleavage of the β-amyloid precursor protein. The ... AB - PEN-2 is a component of the γ-secretase complex, which is involved in the cleavage of the β-amyloid precursor protein. The ...

https://pure.korea.ac.kr/en/publications/pen-2-overexpression-induces-%CE%B3-secretase-protein-and-its-activity

Amyloid Precursor Protein Secretases Medicine & Life Sciences 33% * Secondary Hyperparathyroidism Medicine & Life Sciences 33% ... Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain could be ... N2 - Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain ... AB - Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain ...

https://utsouthwestern.elsevierpure.com/en/publications/klotho-and-chronic-kidney-disease

Amyloid Precursor Protein Secretases Medicine & Life Sciences 89% * Endoplasmic Reticulum Medicine & Life Sciences 69% ... activity by JNK inhibitor SP600125 repressed PS1 transcription and PS1 protein expression by augmenting p53 protein level in SK ... activity by JNK inhibitor SP600125 repressed PS1 transcription and PS1 protein expression by augmenting p53 protein level in SK ... activity by JNK inhibitor SP600125 repressed PS1 transcription and PS1 protein expression by augmenting p53 protein level in SK ...

https://experts.unthsc.edu/en/publications/repression-of-transcription-of-presenilin-1-inhibits-%CE%B3-secretase-

The βA is the amyloid precursor protein (APP) digestion product, released from the cell after secretases proteolysis.This is ... Amyloid-beta peptide Oligomerization Assay. By Innoprot. 10/27/2019. Amyloid-beta peptide Oligomerization Assay is a functional ... Intoxication of neurons with beta-amyloid (1-40) is a useful Alzheimer disease (AD) in vitro model. This model allows evaluate ... Intoxication of neurons with beta-amyloid (1-42) oligomers is a useful Alzheimer disease (AD) in vitro model. This model allows ...

https://innoprot.com/assays/alzheimer/

A beta is a cleavage product of amyloid precursor protein (APP). Certain proteases, called beta-secretases (BACE), are crucial ... beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Activity. beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 ( ... One major hallmark of AD is the deposition of amyloid-beta (A beta) as amyloid plaques in the brain. ...

https://alzped.nia.nih.gov/node/11467/printable/print

Amyloid Precursor Protein(APP). amyloidbeta. amyloidplaques. tauprotein. amyloid casca detheory. amyloidogenic pathway. non- ... secretases. Issue Date: Feb-2020. Publisher: Science Domain International. Citation: Prasad A. S. V. . The Essentials of ... theory held its sway until recent times until the emphasis is shifted to the metabolites of amyloid Beta precursor protein (APP ... Amyloid plaques and Tau tangles, constitute the pathological hallmarks of the brains of the patients suffering from Alzheimers ...

http://imsear.searo.who.int/handle/123456789/200778

2009) Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med 15:377-9 ...

https://grantome.com/grant/NIH/R24-HD050845-04

It is now recognized that a key role is played by BACE1 proteases that cleave amyloid precursor protein (APP) to produce the ... amyloid β42 peptide fragment, ultimately resulting in the formation of amyloid plaques. ... This intense interest in studying the inhibition of γ- and β-secretases for therapeutic intervention in AD patients is ... Figure 1.Cleavage of Amyloid Precursor Protein. Amyloid precursor protein (APP) is sequentially cleaved first by β-secretase ( ...

https://www.sigmaaldrich.com/SG/en/technical-documents/technical-article/protein-biology/enzyme-activity-assays/bace1-assay-kit

... protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor ... This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded ... The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript ... protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. ...

https://pharos.nih.gov/targets/APLP1

BACE1 and presenilin (PS)/γ-secretase are primary proteolytic enzymes responsible for the generation of pathogenic amyloid β-peptides (Aβ) in Alzheimer's disease. (nih.gov)
Aβ peptides are derived from amyloid precursor proteins (APP) through sequential proteolytic cleavage of APP by β-secretases and γ-secretases generating diverse Aβ species. (biolegend.com)
Human Î³- secretase cleaves the transmembrane domains (TMDs) of amyloid precursor protein (APP) into pathologically relevant amyloid -ß peptides (Aßs). (bvsalud.org)
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). (lookformedical.com)
It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. (lookformedical.com)
A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES. (lookformedical.com)
Alcadein cleavages by amyloid beta-precursor protein (APP) alpha- and gamma-secretases generate small peptides, p3-Alcs, indicating Alzheimer disease-related gamma-secretase dysfunction. (tottori-u.ac.jp)
Alzheimer's disease (AD) is characterized by cerebral deposition of β-amyloid (Aβ) peptides, which are generated from amyloid precursor protein (APP) by β- and γ-secretases. (cmu.edu)

In addition, increased amyloid plaques were also found in the hippocampus of 27-OHC-treated mice. (nih.gov)
Beta-Amyloid 1-42 forms a major component of amyloid plaques in neurons of Alzheimer's disease (AD) brains, while beta-Amyloid 1-40 is taken as a negative control of beta-Amyloid 1-42 in most studies. (anaspec.com)
Pyroglutamate-modified (Pyr) beta-Amyloid 3-40 and 11-40 have been described as major compounds in the senile AD plaques. (anaspec.com)
As a result, this protein accumulates in the brain and the characteristic plaques develop. (dzne.de)
Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. (lookformedical.com)
The brains of individuals with AD exhibit characteristic lesions termed senile (or amyloid) plaques, amyloid angiopathy (amyloid deposits in blood vessels) and neurofibrillary tangles. (justia.com)
Amyloid plaques and amyloid angiopathy also characterize the brains of individuals with Trisomy 21 (Down's Syndrome) and Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type (HCHWA-D). (justia.com)
Two types of protein aggregates found in the brain are pathological hallmark of AD: intracellular neurofibrillary tangles and extracellular amyloid plaques (for a recent review see Wong et al. (justia.com)
The extracellular plaques result from elevated levels of an approximately 4.2 kilodalton (kD) protein of about 39-43 amino acids designated the β-amyloid peptide (Aβ) or sometimes βAP, AβP or β/A4 (see, e.g. (justia.com)
One major hallmark of AD is the deposition of amyloid-beta (A beta) as amyloid plaques in the brain. (nih.gov)
Amyloid plaques and Tau tangles, constitute the pathological hallmarks of the brains of the patients suffering from Alzheimer's disease. (who.int)
It is now recognized that a key role is played by BACE1 proteases that cleave amyloid precursor protein (APP) to produce the amyloid β42 peptide fragment, ultimately resulting in the formation of amyloid plaques. (sigmaaldrich.com)
The Aβ is secreted into the extracellular spaces and accumulates to form aggregates, fibrils and eventually amyloid deposits called senile plaques. (sigmaaldrich.com)
Proteolytic cleavage of APP by beta- and gamma-secretases results in the generation of beta amyloid, which is the primary component of senile plaques. (labome.cn)

Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). (igi-global.com)
Beta and gamma secretases cleave APP to form Aβ. (igi-global.com)
The novel disease-modifying approaches involve inhibition of beta and gamma secretases. (igi-global.com)
A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. (igi-global.com)

Sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by secretases (α, β, γ) generates beta-Amyloid peptide fragments. (anaspec.com)
PEN-2 is a component of the γ-secretase complex, which is involved in the cleavage of the β-amyloid precursor protein. (korea.ac.kr)
A beta is a cleavage product of amyloid precursor protein (APP). (nih.gov)
Cleavage of Amyloid Precursor Protein. (sigmaaldrich.com)
The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. (nih.gov)

Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave. (nih.gov)
A thermodynamic investigation of amyloid precursor protein processing by human Î³-secretase. (bvsalud.org)
Our results indicated that (i) human PEN-2 overexpression induced an increase in γ-secretase activity and its proteins, including PS1-CTF, APH-1, and nicastrin, thus production of Aβ-42, (ii) co-transfection of human PEN-2 with both hPS2m and APPsw exerted no more profound effects on the induction of γ-secretase proteins and its activity than did transfection with hPEN-2 alone. (korea.ac.kr)
p53, ZNF237 and Chromodomain helicase DNA-binding protein 3 which are repressors of PS1 transcription, also reduced Ca 2+ leak across ER membrane in SK-N-SH cells but ÎÂ 3 -secretase inhibitor or dominant negative ÎÂ 3 -secretase-specific PS1 mutant (PS1-D257A) had no significant effect. (unthsc.edu)
Aβ is formed by the sequential cleaving of the amyloid precursor protein by the proteases BACE1 (β-secretase or beta-site APP-cleaving enzyme) and γ-secretase (Figure 1). (sigmaaldrich.com)
Therefore, the identification of proteins or compounds that block secretase activity has been and remains a major goal of AD research. (sigmaaldrich.com)
Amyloid precursor protein (APP) is sequentially cleaved first by β-secretase (BACE1) and then by γ-secretase to form soluble amyloid precursor protein β (sAppβ) and the amyloid β42 peptide fragment (Aβ42). (sigmaaldrich.com)
Amyloid Precursor Protein (APP) or Amyloid beta precursor protein functions as a cell surface kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. (labome.cn)
Although retromers and retromer-associated proteins control APP recycling, we show that Rab11 controlled β-secretase endosomal recycling to the plasma membrane and thus affected Aβ production. (cmu.edu)

Christian Haass thus paved the way for therapeutic approaches aimed at preventing the formation of amyloid aggregates or promoting their degradation. (dzne.de)

Through alternative splicing, Klotho protein exists both as a secreted and a membrane form whose extracellular domain could be shed from the cell surface by secretases and released into the circulation to act as endocrine factor. (elsevierpure.com)

Certain proteases, called beta-secretases (BACE), are crucial in the formation of A beta. (nih.gov)

Because β-amyloid peptide (Aβ) is the pathological hallmark of AD, the aim of this study is to verify whether 27-OHC could lead to cognitive impairment through modulating Aβ accumulation and deposition. (nih.gov)
Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. (lookformedical.com)
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. (lookformedical.com)

Intoxication of neurons with beta-amyloid (1-40) is a useful Alzheimer disease (AD) in vitro model. (innoprot.com)
and Appelt, Denah, "Astrocytes Infected with Chlamydia Pneumoniae Demonstrate Altered Expression and Activity of Secretases Involved in the Generation of Β-amyloid Found in Alzheimer Disease" (2019). (pcom.edu)

As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. (lookformedical.com)
Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS. (lookformedical.com)

Hyperphosphorylated isoforms of the microtubule-associated protein tau, which assemble into poorly soluble paired helical filaments, are a central feature of these neurofibrillary tangles (Goedert et al. (justia.com)
Fluorescence intensity of β-amyloid and ELISA-quantified levels of soluble-APP by products revealed temporally similar increases, confirming a BACE1/PSEN1-mediated processing of APP. (pcom.edu)

The gene and protein expression, as well as the enzymatic activity of non-amyloidogenic (ADAM10), and pro-amyloidogenic (BACE1 and PSEN1) secretases were qualitatively and quantitatively assessed. (pcom.edu)
In addition, the formation of toxic amyloid products as an outcome of pro-amyloidogenic APP processing was evaluated through various modalities. (pcom.edu)

IHC staining of Alexa Fluor® 647 anti-β-Amyloid, 1-16 antibody (clone 6E10) on formalin-fixed paraffin-embedded Alzheimer's disease brain tissue. (biolegend.com)
Contrary to what was thought at the time, Haass was able to prove that amyloid is not necessarily a component of pathological processes, but also occurs in the healthy brain. (dzne.de)
According to this, amyloid plays an important role not only in the hereditary form of Alzheimer's disease, by initiating a chain of events that ultimately leads to the death of brain cells. (dzne.de)
But damage to the brain begins many years before - long before symptoms manifest Therefore, therapies that target amyloid continue to be pursued as a possible strategy against Alzheimer's disease. (dzne.de)
Alzheimer's Disease (AD) comprises the accumulation of brain depositions of the beta amyloid (βA). (innoprot.com)
One of the primary causes for the progression of AD is believed to be the accumulation of amyloid beta peptide (Aβ) in the brain. (sigmaaldrich.com)
We recently discovered that Amyloid Precursor Protein (APP) acts as an innate restriction to HIV-1 replication in brain-resident microglia. (northwestern.edu)

It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS. (lookformedical.com)
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues. (lookformedical.com)

This model allows evaluate the capacity of different agents to inhibit the neuronal damage in AD based on the accumulation of neurotoxic amyloid beta peptide. (innoprot.com)

We hypothesized that Chlamydia pneumoniae infection of human astrocytes alters the expression of the amyloid precursor protein (APP)-processing secretases, ADAM10, BACE1, and PSEN1, to promote β-amyloid formation. (pcom.edu)
Relative to that of uninfected astrocytes, BACE1 and PSEN1 protein levels were enhanced by nearly twofold at 48-72 h post-Chlamydia pneumoniae infection. (pcom.edu)

Amyloid Beta: The Foremost Protagonist in Alzheimer's Disease. (igi-global.com)
Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. (igi-global.com)
N-terminally truncated beta-Amyloid 3-40 ad 11-40 , both having a Glu as first residue, are subjected to pyro-glutamination. (anaspec.com)
Pyro-Glu modified beta-Amyloid forms are more resistant to degradation, show higher toxicity and have increased aggregation propensity compared to the non-modified beta-Amyloid equivalent. (anaspec.com)
Se han identificado tres subtipos de secretasa, denominadas alfa, beta y gamma en función de la región de la proteína precursora del amiloide que escinden. (bvsalud.org)
This antibody is reactive to amino acid residue 1-16 of beta amyloid. (biolegend.com)
The epitope lies within amino acids 3-8 of beta amyloid (EFRHDS). (biolegend.com)
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. (lookformedical.com)
Amyloid-beta peptide Oligomerization Assay is a functional cell-based assay to identify inhibitors of amyloid peptide oligomerization process. (innoprot.com)
The amyloid cascade theory held its sway until recent times until the emphasis is shifted to the metabolites of amyloid Beta precursor protein (APP). (who.int)
Recent findings, however, have implicated altered function of ER-mitochondria contact sites and amyloid beta- and/or tau-induced defects in mitochondrial function and dynamics in the pathogenesis of AD, suggesting that mitochondrial defects may act as key mediators in the pathogenesis of AD as well. (biomedcentral.com)

Several studies supporting the "pathogen hypothesis" of AD demonstrate a strong association between pathogens and the production of β-amyloid, the pathologic hallmark of AD. (pcom.edu)

APP and the secretases are membrane associated, but whether membrane trafficking controls Aβ levels is unclear. (cmu.edu)

Therefore, p53, ZNF237, and Chromodomain helicase DNA-binding protein 3 inhibit the function ER Ca 2+ leak channels to regulate both ER and cytoplasmic Ca 2+ levels and may potentially control Ca 2+ -signaling function of PS1. (unthsc.edu)
Here, we performed an RNAi screen of all human Rab-GTPases, which regulate membrane trafficking, complemented with a Rab-GTPase-activating protein screen, and present a road map of the membrane-trafficking events regulating Aβ production. (cmu.edu)
In particular, we are interested in how HIV-1 exploits specialized plus end-binding proteins (+TIPs) to alter MT behavior and regulate infection. (northwestern.edu)

3. Alzheimer's therapeutics: continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond? (nih.gov)

APP is a type I transmembrane protein normally expressed in many different cell types, but particularly abundant in neurons. (justia.com)

Today, it is therefore assumed that the production or degradation of this protein is disturbed in Alzheimer's disease. (dzne.de)

13. Targeting amyloid precursor protein secretases: Alzheimer's disease and beyond. (nih.gov)
We owe him groundbreaking insights into proteins and immune reactions involved in Alzheimer's disease. (dzne.de)

tau phosphorylation assay from Innoprot allows the identification of tau kinase and phosphatase inhibitors and modulators that affect the behaviour or location of tau protein. (innoprot.com)

Our results showed that high nitrogen fertilizer level alters tryptophan metabolism in rice, increasing most amino acid content and protein content in rice. (bvsalud.org)

Haass' research provided important insights into how amyloid is produced from a larger molecule (amyloid precursor protein) under the action of certain enzymes (secretases). (dzne.de)

Therefore, nDNA maintenance and repair mechanisms in the nucleus also play an important role in maintaining mitochondrial fitness, as the mutation of nDNA genes encoding mitochondrial proteins can lead to pathology [ 4 ]. (biomedcentral.com)

Inhibition of basal c-jun-NH2-terminal kinase (JNK) activity by JNK inhibitor SP600125 repressed PS1 transcription and PS1 protein expression by augmenting p53 protein level in SK-N-SH cells (Lee and Das 2008). (unthsc.edu)
This intense interest in studying the inhibition of γ- and β-secretases for therapeutic intervention in AD patients is heightened by the fact that there is no effective drug for the treatment of the disease. (sigmaaldrich.com)

Tau is a group of neuronal microtubule-associated proteins that are formed by alternative mRNA splicing. (innoprot.com)
Neuronal death in PD is associated with defects in mitochondrial function and dynamics arising from mutations in proteins affecting these processes, including α-synuclein, DJ-1, LRRK2, Parkin and Pink1. (biomedcentral.com)

This gene encodes a member of the highly conserved amyloid precursor protein gene family. (nih.gov)
Human mitochondrial DNA (mtDNA) encodes 13 proteins, which are essential for the assembly and function of the mitochondrial respiratory complexes. (biomedcentral.com)
In addition to mtDNA, the nuclear DNA (nDNA) encodes over 1000 mitochondrial proteins, which are required for various metabolic and functional processes. (biomedcentral.com)

Molecular biological and protein chemical analyses have shown that Aβ is a small fragment of a much larger precursor protein, referred to as the β-amyloid precursor protein (APP) (see, e.g. (justia.com)

In fact, Haass later discovered how genetic mutations associated with rare and early forms of Alzheimer's cause overproduction of amyloid. (dzne.de)

Our laboratory initially discovered that HIV-1 capsids bind the kinesin-1 adaptor protein, FEZ1. (northwestern.edu)

A paired RNAi and RabGAP overexpression screen identifies Rab11 as a regulator of β-amyloid production. (cmu.edu)

Although the mechanism of pathogen-induced neurodegeneration of AD remains unclear, astrocytes, a key player of the CNS innate immune response and producer/metabolizer of β-amyloid, have been implicated. (pcom.edu)

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. (lookformedical.com)
Our goal is to understand the molecular basis behind how MTs, regulators of MT dynamics and MT motor proteins function to enable HIV-1 movement to and from the nucleus. (northwestern.edu)

This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. (lookformedical.com)
The amyloid structure has also been found in a number of functional proteins that are unrelated to disease. (lookformedical.com)

Anatomy21

Organisms6

Diseases12

Chemicals and Drugs43

Analytical, Diagnostic and Therapeutic Techniques and Equipment12

Psychiatry and Psychology3

Phenomena and Processes22

Disciplines and Occupations1

Humanities1

Information Science3

Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. (1/1874)

Calpain inhibitor I increases beta-amyloid peptide production by inhibiting the degradation of the substrate of gamma-secretase. Evidence that substrate availability limits beta-amyloid peptide production. (2/1874)

Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. (3/1874)

Protein kinase C and amyloid precursor protein processing in skin fibroblasts from sporadic and familial Alzheimer's disease cases. (4/1874)

Effect of protein kinase A inhibitors on the production of Abeta40 and Abeta42 by human cells expressing normal and Alzheimer's disease-linked mutated betaAPP and presenilin 1. (5/1874)

gamma-Secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid beta peptides of varying length. (6/1874)

Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. (7/1874)

Thimet oligopeptidase cleaves the full-length Alzheimer amyloid precursor protein at a beta-secretase cleavage site in COS cells. (8/1874)

No images available that match "amyloid precursor protein secretases"

Amyloid Precursor Protein Secretases

Amyloid beta-Protein Precursor

Aspartic Acid Endopeptidases

Amyloid beta-Peptides

Alzheimer Disease

Amyloid

Endopeptidases

Presenilin-1

Plaque, Amyloid

Protein Precursors

Mice, Transgenic

Protease Nexins

Serum Amyloid A Protein

Peptide Fragments

Brain

Presenilin-2

Neurons

Protein Processing, Post-Translational

Amyloidosis

Cerebral Amyloid Angiopathy

Presenilins

Molecular Sequence Data

Amino Acid Sequence

tau Proteins

Protein Structure, Tertiary

Membrane Proteins

Nerve Tissue Proteins

Amyloidogenic Proteins

Mutation

Disease Models, Animal

Amyloid Neuropathies

Hippocampus

Cell Line

Cells, Cultured

Islet Amyloid Polypeptide

Cerebral Cortex

LDL-Receptor Related Proteins

Protein Transport

Protein Binding

Mice, Inbred C57BL

Transfection

Maze Learning

Proteolysis

Immunohistochemistry

CHO Cells

Blotting, Western

Cricetinae

Neurofibrillary Tangles

Axonal Transport

Base Sequence

PC12 Cells

ADAM Proteins

Nerve Degeneration

Gene Expression Regulation

Mice, Knockout

Convolvulus

Recombinant Proteins

Serum Amyloid P-Component

Prions

Neuroblastoma

Insulysin

Protease Inhibitors

Receptors, Notch

Neurites

Enzyme-Linked Immunosorbent Assay

Brain Chemistry

RNA, Messenger

Aging

Congo Red

Cell Membrane

Cricetulus

Axons

Neprilysin

Endosomes

Memory Disorders

Recombinant Fusion Proteins

Cell Line, Tumor

Gliosis

Models, Biological

Immunoprecipitation