alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Synucleins: A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.gamma-Synuclein: A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.Impulse Control Disorders: Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification or release of tension at the time of committing the act.beta-Synuclein: A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Protein D-Aspartate-L-Isoaspartate Methyltransferase: A PROTEIN O-METHYLTRANSFERASE that recognizes and catalyzes the methyl esterification of ISOASPARTIC ACID and D-ASPARTIC ACID residues in peptides and proteins. It initiates the repair of proteins damaged by the spontaneous decomposition of normal L-aspartic acid and L-asparagine residues.Lewy Bodies: Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.Nerve Tissue ProteinsParkinsonian Disorders: A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.Integrin alpha3beta1: Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.Integrin alpha4: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.Integrin alpha5beta1: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.Integrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.Integrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Integrin alpha5: This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.Integrin alpha1beta1: Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Integrin alpha6beta1: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Access to Information: Individual's rights to obtain and use information collected or generated by others.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.National Institutes of Health (U.S.): An operating division of the US Department of Health and Human Services. It is concerned with the overall planning, promoting, and administering of programs pertaining to health and medical research. Until 1995, it was an agency of the United States PUBLIC HEALTH SERVICE.Research Report: Detailed account or statement or formal record of data resulting from empirical inquiry.PrimatesAging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Gene Duplication: Processes occurring in various organisms by which new genes are copied. Gene duplication may result in a MULTIGENE FAMILY; supergenes or PSEUDOGENES.Multiple System Atrophy: A syndrome complex composed of three conditions which represent clinical variants of the same disease process: STRIATONIGRAL DEGENERATION; SHY-DRAGER SYNDROME; and the sporadic form of OLIVOPONTOCEREBELLAR ATROPHIES. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord. (From Adams et al., Principles of Neurology, 6th ed, p1076; Baillieres Clin Neurol 1997 Apr;6(1):187-204; Med Clin North Am 1999 Mar;83(2):381-92)Metencephalon: The anterior portion of the developing hindbrain. It gives rise to the CEREBELLUM and the PONS.Lewy Body Disease: A neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. The neuropsychiatric manifestations tend to precede the onset of bradykinesia, MUSCLE RIGIDITY, and other extrapyramidal signs. DELUSIONS and visual HALLUCINATIONS are relatively frequent in this condition. Histologic examination reveals LEWY BODIES in the CEREBRAL CORTEX and BRAIN STEM. SENILE PLAQUES and other pathologic features characteristic of ALZHEIMER DISEASE may also be present. (From Neurology 1997;48:376-380; Neurology 1996;47:1113-1124)Journalism, Medical: The collection, writing, and editing of current interest material on topics related to biomedicine for presentation through the mass media, including newspapers, magazines, radio, or television, usually for a public audience such as health care consumers.Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders.

Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro. (1/1546)

alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with distinct morphologies under defined in vitro conditions. Immunogold labeling demonstrates that the central region of all these filaments are more robustly labeled than the N-terminal or C-terminal regions, suggesting that the latter regions are buried within the filaments. Since in vitro generated alpha-synuclein filaments resemble the major ultrastructural elements of authentic Lewy bodies that are hallmark lesions of Parkinson's disease, we propose that self-aggregating alpha-synuclein is the major subunit protein of these filamentous lesions.  (+info)

Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation. (2/1546)

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD, but their pathogenic mechanism is not understood. Here we show that both wild type and mutant alpha-synuclein form insoluble fibrillar aggregates with antiparallel beta-sheet structure upon incubation at physiological temperature in vitro. Importantly, aggregate formation is accelerated by both PD-linked mutations. Under the experimental conditions, the lag time for the formation of precipitable aggregates is about 280 h for the wild type protein, 180 h for the A30P mutant, and only 100 h for the A53T mutant protein. These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations.  (+info)

Copper(II)-induced self-oligomerization of alpha-synuclein. (3/1546)

alpha-Synuclein is a component of the abnormal protein depositions in senile plaques and Lewy bodies of Alzheimer's disease (AD) and Parkinson's disease respectively. The protein was suggested to provide a possible nucleation centre for plaque formation in AD via selective interaction with amyloid beta/A4 protein (Abeta). We have shown previously that alpha-synuclein has experienced self-oligomerization when Abeta25-35 was present in an orientation-specific manner in the sequence. Here we examine this biochemically specific self-oligomerization with the use of various metals. Strikingly, copper(II) was the most effective metal ion affecting alpha-synuclein to form self-oligomers in the presence of coupling reagents such as dicyclohexylcarbodi-imide or N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. The size distribution of the oligomers indicated that monomeric alpha-synuclein was oligomerized sequentially. The copper-induced oligomerization was shown to be suppressed as the acidic C-terminus of alpha-synuclein was truncated by treatment with endoproteinase Asp-N. In contrast, the Abeta25-35-induced oligomerizations of the intact and truncated forms of alpha-synuclein were not affected. This clearly indicated that the copper-induced oligomerization was dependent on the acidic C-terminal region and that its underlying biochemical mechanism was distinct from that of the Abeta25-35-induced oligomerization. Although the physiological or pathological relevance of the oligomerization remains currently elusive, the common outcome of alpha-synuclein on treatment with copper or Abeta25-35 might be useful in understanding neurodegenerative disorders in molecular terms. In addition, abnormal copper homoeostasis could be considered as one of the risk factors for the development of disorders such as AD or Parkinson's disease.  (+info)

alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease. (4/1546)

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major components of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD. alpha-Synuclein fibrils similar to the Lewy body filaments can be formed in vitro, and we have shown recently that both PD-linked mutations accelerate their formation. This study addresses the mechanism of alpha-synuclein aggregation: we show that (i) it is a nucleation-dependent process that can be seeded by aggregated alpha-synuclein functioning as nuclei, (ii) this fibril growth follows first-order kinetics with respect to alpha-synuclein concentration, and (iii) mutant alpha-synuclein can seed the aggregation of wild type alpha-synuclein, which leads us to predict that the Lewy bodies of familial PD patients with alpha-synuclein mutations will contain both, the mutant and the wild type protein. Finally (iv), we show that wild type and mutant forms of alpha-synuclein do not differ in their critical concentrations. These results suggest that differences in aggregation kinetics of alpha-synucleins cannot be explained by differences in solubility but are due to different nucleation rates. Consequently, alpha-synuclein nucleation may be the rate-limiting step for the formation of Lewy body alpha-synuclein fibrils in Parkinson's disease.  (+info)

alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. (5/1546)

alpha-Synuclein has been implicated in the pathophysiology of many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Mutations in alpha-synuclein cause some cases of familial PD (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that alpha-synuclein shares physical and functional homology with 14-3-3 proteins, which are a family of ubiquitous cytoplasmic chaperones. Regions of alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition, alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to associate with 14-3-3, including protein kinase C, BAD, and extracellular regulated kinase, but not Raf-1. We also show that overexpression of alpha-synuclein inhibits protein kinase C activity. The association of alpha-synuclein with BAD and inhibition of protein kinase C suggests that increased expression of alpha-synuclein could be harmful. Consistent with this hypothesis, we observed that overexpression of wild-type alpha-synuclein is toxic, and overexpression of alpha-synuclein containing the A53T or A30P mutations exhibits even greater toxicity. The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases.  (+info)

Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies. (6/1546)

Alzheimer's disease and Parkinson's disease are the most common neurodegenerative diseases. They are characterized by the degeneration of selected populations of nerve cells that develop filamentous inclusions before degeneration. The neuronal inclusions of Alzheimer's disease are made of the microtubule-associated protein tau, in a hyperphosphorylated state. Recent work has shown that the filamentous inclusions of Parkinson's disease are made of the protein alpha-synuclein and that rare, familial forms of Parkinson's disease are caused by missense mutations in the alpha-synuclein gene. Besides Parkinson's disease, the filamentous inclusions of two additional neurodegenerative diseases, namely dementia with Lewy bodies and multiple system atrophy, have also been found to be made of alpha-synuclein. Abundant filamentous tau inclusions are not limited to Alzheimer's disease. They are the defining neuropathological characteristic of frontotemporal dementias such as Pick's disease, and of progressive supranuclear palsy and corticobasal degeneration. The recent discovery of mutations in the tau gene in familial forms of frontotemporal dementia has provided a direct link between tau dysfunction and dementing disease. The new work has established that tauopathies and alpha-synucleinopathies account for most late-onset neurodegenerative diseases in man. The formation of intracellular filamentous inclusions might be the gain of toxic function that leads to the demise of affected brain cells.  (+info)

alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. (7/1546)

alpha-Synuclein has been implicated in the pathogenesis of several neurodegenerative disorders based on the direct linking of missense mutations in alpha-synuclein to autosomal dominant Parkinson's disease and its presence in Lewy-like lesions. To gain insight into alpha-synuclein functions, we have investigated whether it binds neuronal proteins and modulates their functional state. The microtubule-associated protein tau was identified as a ligand by alpha-synuclein affinity chromatography of human brain cytosol. Direct binding assays using (125)I-labeled human tau40 demonstrated a reversible binding with a IC(50) about 50 pM. The interacting domains were localized to the C terminus of alpha-synuclein and the microtubule binding region of tau as determined by protein fragmentation and the use of recombinant peptides. High concentrations of tubulin inhibited the binding between tau and alpha-synuclein. Functionally, alpha-synuclein stimulated the protein kinase A-catalyzed phosphorylation of tau serine residues 262 and 356 as determined using a phospho-epitope-specific antibody. We propose that alpha-synuclein modulates the phosphorylation of soluble axonal tau and thereby indirectly affects the stability of axonal microtubules.  (+info)

The genetics of disorders with synuclein pathology and parkinsonism. (8/1546)

Despite being considered the archetypal non-genetic neurological disorder, genetic analysis of Parkinson's disease has shown that there are at least three genetic loci. Furthermore, these analyses have suggested that the phenotype of the pathogenic loci is wider than simple Parkinson's disease and may include Lewy body dementia and some forms of essential tremor. Identification of alpha-synuclein as the first of the loci involved in Parkinson's disease and the identification of this protein in pathological deposits in other disorders has led to the suggestion that it may share pathogenic mechanisms with multiple system atrophy, Alzheimer's disease and prion disease and that these mechanisms are related to a synuclein pathway to cell death. Finally, genetic analysis of the synuclein diseases and the tau diseases may indicate that this synuclein pathway is an alternative to the tau pathway to cell death.  (+info)

Toxicity of human alpha-synuclein when expressed in simple organisms can be suppressed by overexpression of endoplasmic reticulum (ER)-to-Golgi transport machinery, suggesting that inhibition of constitutive secretion represents a fundamental cause of the toxicity. Whether similar inhibition in mammals represents a cause of familial Parkinsons disease has not been established. We tested elements of this hypothesis by expressing human alpha-synuclein in mammalian kidney and neuroendocrine cells and assessing ER-to-Golgi transport. Overexpression of wild type or the familial disease-associated A53T mutant alpha-synuclein delayed transport by up to 50%; however, A53T inhibited more potently. The secretory delay occurred at low expression levels and was not accompanied by insoluble alpha-synuclein aggregates or mistargeting of transport machinery, suggesting a direct action of soluble alpha-synuclein on trafficking proteins. Co-overexpression of ER/Golgi arginine soluble N-ethylmaleimide-sensitive factor
TY - JOUR. T1 - Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage. AU - Paiva, Isabel. AU - Pinho, Raquel. AU - Pavlou, Maria Angeliki. AU - Hennion, Magali. AU - Wales, Pauline. AU - Schütz, Anna Lena. AU - Rajput, Ashish. AU - Szego, Éva M.. AU - Kerimoglu, Cemil. AU - Gerhardt, Ellen. AU - Rego, Ana Cristina. AU - Fischer, André. AU - Bonn, Stefan. AU - Outeiro, Tiago F.. PY - 2017/6/15. Y1 - 2017/6/15. N2 - Alpha-synuclein (aSyn) is considered a major culprit in Parkinsons disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional ...
Title:A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies. VOLUME: 19 ISSUE: 6. Author(s):Larisa Ryskalin, Carla L. Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella and Francesco Fornai*. Affiliation:Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126 Pisa, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126 Pisa, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia. Keywords:Alpha synuclein, synucleinopathies, alpha synuclein aggregates, loss-of-function, co-chaperonine, neurodegeneration, neuroprotection.. Abstract:Alpha synuclein (α-syn) belongs to a class of proteins which ...
Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. Alpha-synuclein is encoded by the SNCA gene in humans and is mainly expressed in the cerebral neocortex, hippocampus, nigra, thalamus, and metencephalon, with the majority of the protein localizing to the presynaptic terminal and nucleus of neuron cells. The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinsons disease, Lewy body dementia (associated with both Alzheimers and Parkinsons disease), and multiple system atrophy. Mutations in the SNCA gene have been associated with the pathogenesis of Parkinson disease.. ...
Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. Alpha-synuclein is encoded by the SNCA gene in humans and is mainly expressed in the cerebral neocortex, hippocampus, nigra, thalamus, and metencephalon, with the majority of the protein localizing to the presynaptic terminal and nucleus of neuron cells. The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinsons disease, Lewy body dementia (associated with both Alzheimers and Parkinsons disease), and multiple system atrophy. Mutations in the SNCA gene have been associated with the pathogenesis of Parkinson disease.. ...
Parkinsons disease (PD) is characterized by a progressive loss of midbrain dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies. Mutations in several genes including alpha-synuclein and parkin have been linked to familial PD. The loss of parkins E3-ligase activity leads to dopaminergic neuronal degeneration in early-onset autosomal recessive juvenile parkinsonism, suggesting a key role of parkin for dopamine neuron survival. To evaluate the potential neuroprotective role of parkin in the pathogenesis of PD, we tested whether overexpression of wild-type rat parkin could protect against the toxicity of mutated human A30P alpha-synuclein in a rat lentiviral model of PD. Animals overexpressing parkin showed significant reductions in alpha-synuclein-induced neuropathology, including preservation of tyrosine hydroxylase-positive cell bodies in the substantia nigra and sparing of tyrosine hydroxylase-positive nerve terminals in the striatum. The parkin-mediated neuroprotection was
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. It is abundant in the brain while smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with phospholipids and proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function ...
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. It is abundant in the brain while smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with phospholipids and proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function ...
We have produced a panel of 32 unique monoclonal antibodies that recognize common structural elements in amyloid aggregates, like the alpha-synuclein aggregates that are believed to play an important role in PD pathogenesis. Although these antibodies were originally produced against Abeta amyloid from Alzheimer s disease, we found that many of them recognize common or generic epitopes (or antibody binding sites) that occur on amyloid aggregates from a number of different amyloids made from different protein sequences. For some of these antibodies, we have already shown that interact with alpha-synuclein aggregates in vitro. In this project, we will test the immunoreactivity of all of the antibodies against alpha-synuclein oligomers and fibrils. We will also test whether any of the antibodies can detect pathological oligomers in human PD brain. Antibodies that react with pathological amyloid aggregates in brain would represent candidates for therapeutic development.. Relevance to ...
Objective/Rationale: Mounting evidence indicates a crucial role of pathological aggregates of the protein alpha-synuclein in Parkinsons disease (PD). Small aggregates termed oligomers seems to be toxic for nerve cells. Moreover, prion-like spread of pathological alpha-synuclein aggregation may cause progressive degeneration of brain areas. We recently developed the novel oligomer modulator anle138b that inhibits the formation of pathological alpha-synuclein oligomers and has shown therapeutic efficacy in several models of PD.Project Description:We will test anle138b in a novel, large PD model. First, we will test which doses are required to obtain relevant levels of anle138b in blood and tissue (
Findings from human patients, yeast and a mouse model imply that defects in polyamine pathway play a role in Parkinsons disease pathogenesis, suggesting that existing drugs may be able to slow progression of the disease, according to a study published Sept. 13 in an early online edition of Proceedings of the National Academy of Sciences.
An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinsons disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We
Accumulating evidence suggests that the lesions of Parkinsons disease (PD) expand due to transneuronal spreading of fibrils composed of misfolded alpha-synuclein (a-syn), over the course of 5-10 years. However, the precise mechanisms and the processes underlying the spread of these fibril seeds have not been clarified in vivo. Here, we investigated the speed of a-syn transmission, which has not been a focus of previous a-syn transmission experiments, and whether a-syn pathologies spread in a neural circuit-dependent manner in the mouse brain. We injected a-syn preformed fibrils (PFFs), which are seeds for the propagation of a-syn deposits, either before or after callosotomy, to disconnect bilateral hemispheric connections. In mice that underwent callosotomy before the injection, the propagation of a-syn pathology to the contralateral hemisphere was clearly reduced. In contrast, mice that underwent callosotomy 24 h after a-syn PFFs injection showed a-syn pathology similar to that seen in mice without
Spark Therapeutics Enters into Definitive Merger Agreement with Roche Spark Therapeutics announced that it has entered into a definitive merger agreement for Roche to fully acquire Spark Therapeutics at a price of $114.50 per share in an all-cash transaction. [Spark Therapeutics, Inc.] Press Release AbbVie and Voyager Therapeutics Announce Collaboration to Develop Vectorized Antibodies to Treat Parkinsons Disease and Other Synucleinopathies AbbVie and Voyager Therapeutics, Inc. announced an exclusive, global strategic collaboration and option agreement to develop and commercialize vectorized antibodies directed at pathological species of alpha-synuclein for the potential treatment of Parkinsons disease and other diseases (synucleinopathies) characterized by the abnormal accumulation of misfolded alpha-synuclein protein. [AbbVie Inc.] Press Release CRISPR Therapeutics and StrideBio Expand Exclusive Development and Option Agreement CRISPR Therapeutics and StrideBio, Inc. announced that a ...
of Lewy Neurites].. I have previously demonstrated to you (with the most excellent Immunostains of Paula at Excalibur Labs) that:. 1. Lewy bodies are marked with Rabbit antibodies to human Alpha Synuclein. 2. Lewy neurites are marked with rabbit antibodies to human Alpha Synuclein. 3. Nematode larval worms contain immunorective proteins to Human Alpha Synuclein. 4. Nematode worms are endowed with their own neurons and their own Glial cells. 5. Synuclein proteins (but not necessarily the toxic variant of Alpha synuclein) are incumbent in Synaptic Structure, and these are located between the Dendritic/Synaptic button apparatus and the Nucleus of the neuron. 6. Borrelia burgdorferi is an EndoSymbiont microbe which dwells inside of the bodies of select nematode worms, larvae, and worm eggs too.. 7. Borrelia burgdorferi might be endowed with a protein which is immune-reactive to the toxic variant of Alpha Synuclein or Borrelia spirochetes may absorb this protein or Borrelia spriochetes may absorb ...
of Lewy Neurites].. I have previously demonstrated to you (with the most excellent Immunostains of Paula at Excalibur Labs) that:. 1. Lewy bodies are marked with Rabbit antibodies to human Alpha Synuclein. 2. Lewy neurites are marked with rabbit antibodies to human Alpha Synuclein. 3. Nematode larval worms contain immunorective proteins to Human Alpha Synuclein. 4. Nematode worms are endowed with their own neurons and their own Glial cells. 5. Synuclein proteins (but not necessarily the toxic variant of Alpha synuclein) are incumbent in Synaptic Structure, and these are located between the Dendritic/Synaptic button apparatus and the Nucleus of the neuron. 6. Borrelia burgdorferi is an EndoSymbiont microbe which dwells inside of the bodies of select nematode worms, larvae, and worm eggs too.. 7. Borrelia burgdorferi might be endowed with a protein which is immune-reactive to the toxic variant of Alpha Synuclein or Borrelia spirochetes may absorb this protein or Borrelia spriochetes may absorb ...
Alpha-Synuclein (aSyn) is a 140 amino acid, intrinsically disordered protein that adopts an extended amphipathic alpha-helical structure upon binding the membrane. aSyn is the major proteinaceous component of insoluble fibrillar Lewy bodies, a hallmark of Parkinsons disease (PD). The precise roles of both native and pathological forms of aSyn remain unclear. However, the interaction of aSyn with cellular membranes is now thought to be critical to its native function, and potentially to its role in PD. In vivo studies with overexpressed aSyn shows a stalling of vesicle fusion at the plasma membrane, whereas in vitro studies of small lipid vesicles and aSyn demonstrate an inhibition of vesicle fusion. In addition, numerous biophysical studies have identified potential curvature sensing and curvature inducing characteristics for aSyn, however the mechanism behind these processes is not well understood. The work in this thesis explores the membrane remodeling capacity of aSyn using a combination of ...
Parkinsons disease - characterized by tremors, rigidity, difficulty walking and other symptoms - is caused by the destruction of brain cells that produce the neurotransmitter dopamine. In recent years researchers at several centers have been studying the role of alpha-synuclein accumulations in dopamine-producing neurons, observed in patients with both inherited and sporadic Parkinsons disease. MGH-MIND investigators have discovered that, in Parkinsons, the alpha-synuclein molecule folds abnormally and form aggregates called inclusion bodies. Such inclusions of other abnormal proteins are seen in several disorders, but whether inclusions are toxic or protective to neurons has been controversial.. In a paper published last year in the Proceedings of the National Academy of Sciences, a research team led by Kazantsev analyzed ways to reduce the size of inclusions containing misfolded versions of alpha-synuclein or of the Huntingtons disease-associated protein huntingtin. They found that a ...
Alpha synuclein is normally found in neurons, particularly at synapses. When it misfolds, it begins to cause damage. To directly test the gut to brain hypothesis, the researchers injected misfolded alpha synuclein fibrils directly into the muscular wall of the gut in mice, at the point where the stomach empties into the first part of the small intestine, called the duodenum. These fibrils began interacting with the alpha synuclein found in local nerves in the gut, triggering a further misfolding process.. One month later, the researchers found misfolded alpha synuclein in the brain, specifically at the point at which the vagus nerve originates. Within 3 months, misfolded alpha synuclein could be found in other parts of the brain, including the substantia nigra, the main dopamine centre which is involved in movement, and by 7 months, alpha synuclein could clearly be seen in this region.. The team then addressed the effects of cutting the vagus nerve in mice that had been injected with preformed ...
Tytuł projektu: Rozbudowa i przekształcenie bibliograficznej bazy danych AGRO w bazę bibliograficzno-abstraktową z wykorzystaniem oprogramowania YADDA. Nr umowy: POIG 02.03.02-00-031/09 (okres realizacji 2009-2013 ...
Our findings further support the causative role of soluble amyloid oligomers in triggering neurodegeneration and shed light into the mechanisms by which these species cause neuronal damage, which, we show here, can be amenable to modulation through the use of metal chelation.
AURORA, Colo. (Dec. 22, 2017) - While vigorous exercise on a treadmill has been shown to slow the progression of Parkinsons disease in patients, the molecular reasons behind it have remained a mystery.. But now scientists at the University of Colorado Anschutz Medical Campus may have an answer.. For the first time in a progressive, age-related mouse model of Parkinsons, researchers have shown that exercise on a running wheel can stop the accumulation of the neuronal protein alpha-synuclein in brain cells.. The work, published Friday in the journal PLOS ONE, was done by Wenbo Zhou, PhD, research associate professor of medicine and Curt Freed, MD, professor of medicine and division head of the Division of Clinical Pharmacology and Toxicology at the CU School of Medicine.. The researchers said clumps of alpha-synuclein are believed to play a central role in the brain cell death associated with Parkinsons disease. The mice in the study, like humans, started to get Parkinsons symptoms in ...
In this special issue of Neuropathology and Applied Neurobiology on synucleinopathies, leading investigators provide an overview of this vibrating field. A basic understanding is at hand and it appears increasingly likely that safe and effective mechanism-based therapies for synucleinopathies will be developed. They will probably be aimed at prevention rather than at treating already existing disease. PD stands out among neurodegenerative diseases, in that an effective symptomatic therapy in the form of dopamine replacement already exists. In the first contribution, Roger Barker and Caroline Williams-Gray provide a comprehensive overview of the clinical features of PD and compare them with those of other synucleinopathies (1). In the second article, Nadia Stefanova and Gregor Wenning focus on the rarer, but more aggressive, MSA, which is divided into parkinsonian (MSA-P) and cerebellar (MSA-C) forms, with many cases having features of both (mixed-type MSA) (2). Autonomic dysfunction is a major ...
When misfolded, the protein alpha-synuclein becomes toxic to neurons and is a key pathological culprit in Parkinsons. It is therefore an important target for disease-modification. Immunotherapy in Parkinsons attempts to use immune cells, and specifically the antibodies they generate, to target misfolded alpha-synuclein to inactivate it.
Lewy bodies of a-synuclein protein are prominent characteristics in the Parkinsons disease (PD) pathology. The mechanism of Lewy body formation and consequent cytotoxicity was studied by Brandis et al. (2006) in a newly developed model organism of fission yeast. Though, the level of a-synuclein expression studied was either high or low, the wild-type and A53T familial mutant of a-synuclein followed the nucleation polymerization theory in the process of misfolding and aggregating. At high concentration, a-synuclein formed cytoplasmic aggregates in a concentration and time-dependent manner. However, these aggregates appeared to be independent of cytotoxicity. In this current study, the fission yeast model is used again but to evaluate a-synuclein misfolding, aggregation, and non-toxic properties when expression is moderate. The results indicate moderate a-synuclein expression to obey the nucleation polymerization model. In light of this study, a-synuclein aggregation requires a necessary threshold
Parkinsons disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)-containing intraneuronal inclusions-Lewy bodies (LBs) and Lewy neurites (LNs)-in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other brain regions. However, a cause-and-effect relationship between LB/LN formation and neurodegeneration remains unclear. Indeed, whether LB/LNs are toxic or represent a neuroprotective response has been contentious. Luk et al. (p. 949) injected α-Syn fibrils generated from recombinant mouse α-Syn protein into the dorsal striatum of wild-type mice and found that misfolded α-Syn caused the formation of PD-like LB/LNs and subsequent cell-to-cell transmission of pathologic α-Syn to anatomically interconnected regions, including the SNpc. Furthermore, the formation of LB/LNs and their accumulation in SNpc resulted in the progressive loss of these dopaminergic neurons, reduced dopamine innervations to ...
Insoluble and fibrillar forms of α-synuclein are the major components of Lewy bodies, a hallmark of several sporadic and inherited neurodegenerative diseases known as synucleinopathies. α-Synuclein is a natural unfolded and aggregation-prone protein that can be degraded by the ubiquitin-proteasomal system and the lysosomal degradation pathways. α-Synuclein is a target of the main cellular proteolytic systems, but it is also able to alter their function further, contributing to the progression of neurodegeneration. Aging, a major risk for synucleinopathies, is associated with a decrease activity of the proteolytic systems, further aggravating this toxic looping cycle. Here, the current literature on the basic aspects of the routes for α-synuclein clearance, as well as the consequences of the proteolytic systems collapse, will be discussed. Finally, particular focus will be given to the sirtuinss role on proteostasis regulation, since their modulation emerged as a promising therapeutic strategy to
Detect and quantitate human Alpha-synuclein in biological fluids such as serum, plasma, cerebrospinal fluid and cell culture supernatants using a homogeneous AlphaLISA no-wash assay.
The alpha-synuclein (alpha-syn) protein is clearly implicated in Parkinsons disease (PD). Mutations or triplication of the alpha-syn gene leads to early onset PD, possibly by accelerating alpha-syn oligomerization. alpha-syn interacts with lipids, and this membrane binding activity may relate to it …
Parkinsons disease is the second most common neurodegenerative disorder[31] and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinsons disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinsons disease. The mechanism by which the brain cells in Parkinsons are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteasome. This protein accumulation forms proteinaceous ...
Parkinsons disease is the second most common neurodegenerative disorder[31] and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinsons disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinsons disease. The mechanism by which the brain cells in Parkinsons are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteasome. This protein accumulation forms proteinaceous ...
Health,... This news release is available in a onClick NewPopupWindow(t...In Parkinsons disease the protein alpha-synuclein aggregates and a...Parkinsons disease is a disorder of the nervous system. It typically ...At the present no cure exists for Parkinsons disease although sympt...,Proteins,in,migration,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Project Description Primary Supervisor: Prof Flaviano Giorgini (Dept Genetics) Secondary Supervisor: Dr Vincenzo Marra (Dept Neuroscience, Psychology, & Behaviour) Parkinsons disease (PD), the second most common neurodegenerative disorder, is characterized by loss of dopaminergic neurons and the accumulation of misfolded alpha-synuclein (aSyn). Aberrant aSyn aggregation and consequent perturbed vesicular trafficking likely contribute to neurodegeneration. Rab…
AIMS: Gastrointestinal (GI) α-synuclein (aSyn) detection as a potential biomarker of Parkinsons disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically well-characterized cohort of PD patients and healthy controls (HC). METHODS: With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn. RESULTS: A total of 163 tissue blocks were collected from 51 PD patients (113 blocks) and 21 HC (50 blocks). In 31 PD patients, biopsies were taken before the PD diagnosis (Prodromal); while in 20 PD patients biopsies were obtained after diagnosis (Manifest). The majority of tissues blocks were from
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Alpha-synuclein is expressed principally in the central nervous system (brain) but is also expressed in low concentrations in a variety of tissues…
Alpha-synuclein is expressed principally in the central nervous system (brain) but is also expressed in low concentrations in a variety of tissues…
购买我们的重组人alpha Synuclein (deletion )蛋白。Ab51178为蛋白片段,在大肠杆菌中生产并经过SDS-PAGE实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。
Hi LuSampieri,. It seems like many commonly used immortalized human cells, including HEK293 and HeLa, do express alpha synuclein.. Check out this paper for more details.. Good luck.. ...
购买我们的重组人alpha Synuclein (mutated E46 K)蛋白。Ab51188为全长蛋白,在大肠杆菌中生产并经过SDS-PAGE实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。
Pathogenic aggregation of α-Synuclein \(αSyn) is implicated in familial and sporadic Parkinson disease \(PD) and several other synucleinopathies. Choosing non-denaturing conditions, we developed a several purification schemes in order to obtain αSyn from human erythrocytes, enabling researchers ...
January 25, 2017. Parkinsons disease (PD) and other "synucleinopathies" are known to be linked to the misfolding of alpha-synuclein protein in neurons. Less clear is how this misfolding relates to the growing number of genes implicated in PD through analysis of human genetics. Two new studies from researchers affiliated with Whitehead Institute and Massachusetts Institute of Technology explain how they used a suite of novel biological and computational methods to shed light on the question.. ...
PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to ...
Rabbit polyclonal Alpha-synuclein (phospho Y133) antibody. Validated in WB, ICC/IF and tested in Mouse, Rat, Human. Immunogen corresponding to synthetic peptide.
Rabbit polyclonal Alpha-synuclein (phospho S129) antibody. Validated in WB, ELISA, IHC, ICC/IF and tested in Mouse, Human. Cited in 36 publication(s). Independently reviewed in 4 review(s). Immunogen…
Putcha P, Danzer KM, Kranich LR, Scott A, Silinski M, Mabbett S, Hicks CD, Veal JM, Steed PM, Hyman BT, McLean PJ. Brain-permeable small-molecule inhibitors of Hsp90 prevent alpha-synuclein oligomer formation and rescue alpha-synuclein-induced toxicity ...
PHILADELPHIA - Using powerful, newly developed cell culture and mouse models of sporadic Parkinsons disease (PD), a team of researchers from the Perelman School of Medicine at the University of Pennsylvania, has demonstrated that immunotherapy with specifically targeted antibodies may block the development and spread of PD pathology in the brain. By intercepting the distorted and misfolded alpha-synuclein (α-syn) proteins that enter and propagate in neurons, creating aggregates, the researchers prevented the development of pathology and also reversed some of the effects of already-existing disease. The α-syn clumps, called Lewy bodies, eventually kill affected neurons, which leads to clinical PD. Their work appears this week in Cell Reports. Earlier studies by senior author Virginia M.Y. Lee, PhD, and her colleagues at Penns Center for Neurodegenerative Disease Research (CNDR) had demonstrated a novel pathology of PD in which misfolded α-syn fibrils initiate and propagate Lewy bodies via ...
What role does alpha-synuclein play in Parkinsons disease? The proteins involvement has been controversial because its not clear whether buildup of the abnormal version of the protein actually causes the onset of the disease.. But in a paper just out in Science, researchers demonstrated that healthy mice developed the telltale signs of the Parkinsons disease when their brains were injected with the abnormal protein. This suggests that the buildup of abnormal alpha-synuclein could cause the disease.. Virginia Lee at the University of Pennsylvania Perelman School of Medicine, who spearheaded the research, explains that there has been a lack of evidence to show a direct link between the accumulation of alpha-synuclein in deposits known as Lewy bodies and a loss of dopaminergic neurons. Dopaminergic neurons produce dopamine; the loss of dopamine causes the movement disorder in Parkinsons patients.. Lee says there havent been any animal models that connect Lewy bodies to dopaminergic neuron ...
There are many things you dont want gathering in large numbers, including locusts, rioters, and brain proteins. Our nerve cells contain many proteins that typically live in solitude, but occasionally gather in their thousands to form large insoluble clumps. These clumps can be disastrous. They can wreck neurons, preventing them from firing normally and eventually killing them.. Such clumps are the hallmarks of many brain diseases. The neurons of Alzheimers patients are riddled with tangles of a protein called tau. Those of Parkinsons patients contain bundles, or fibrils, of another protein called alpha-synuclein. The fibrils gather into even larger clumps called Lewy bodies.. Now, Laura Volpicelli-Daley from the University of Pennsylvania School of Medicine has confirmed that the alpha-synuclein fibrils can spread. Once theyve entered a new neuron, they can corrupt the local proteins, changing their shape and gathering them into fresh Lewy bodies. Theyre like gangs that travel from town to ...
The first author of the study is Shuchi Mittal, of Harvard Medical School, and the findings were published in the journal Science.. The research has several parts. First, the scientists conducted studies in cell cultures. Specifically, they searched for compounds that may downregulate the genetic expression of alpha-synuclein, which is the clumpy brain protein that builds up in excess and leads to Parkinsons symptoms. Using small molecule screening, the researchers found that a class of drugs called beta2-adrenoreceptor agonists has the potential to reduce alpha-synuclein expression. Then, they tested these drugs in mice and stem cells. The preliminary results suggested that two kinds of beta2-adrenergic drugs may have opposing effects on the risk of Parkinsons disease.. This prompted the team to further zoom in on these two types of beta2-adrenergic compounds: a beta2-adrenergic agonist called salbutamol (used for treating asthma), and beta2-adrenergic antagonists called beta-blockers (used ...
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature ... alpha-synuclein was discovered to be the major component of Lewy bodies within brain cells of PD patients; according to the ... alpha-synuclein. Lazzarini worked with the Italian Instituto de Scienze Neurologiche to get blood samples from the family ... that fragments of alpha-synuclein bind to other proteins to form the Lewy body, an insoluble proteinaceous material ...
The NIH team and a team led by Maria Spillantini reported on alpha-synuclein deposits in Lewy bodies as well as alpha-synuclein ... Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997). "Alpha-synuclein in Lewy bodies". Nature. 388 ( ... Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998). "Alpha synuclein in neurodegenerative disorders ... 1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045-7. doi ...
... alpha-synuclein. Within days of the publication of the PARK1 findings, alpha-synuclein was discovered to be the major component ... Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature ... Schulz-Schaeffer WJ (August 2010). "The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, ... "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045-7. doi:10.1126 ...
She is most noted for identifying the protein alpha-synuclein as the major component of Lewy bodies, the characteristic protein ... Spillantini, MG; Schmidt, ML; Lee, VM; Trojanowski, JQ; Jakes, R; Goedert, M (Aug 28, 1997). "Alpha-synuclein in Lewy bodies". ... In particular her work studies the role of microtubule-associated protein tau and alpha-synuclein aggregation in the ...
"Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct". Science (New York, N.Y.). 294 ( ... "Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein". Neuron. 34 (4): ... Wild-type alpha-synuclein fibrils are known to be the primary component of Lewy bodies, which are found in the brain of ... A53T alpha-synuclein has also been linked to early on-set familial Parkinson's disease. Advancements in technology have allowed ...
Preclinical research also targets alpha-synuclein. Selegiline is in a group of medications called monoamine oxidase type B (MAO ...
Preclinical research also targets alpha-synuclein. A vaccine that primes the human immune system to destroy alpha-synuclein, ... In 1997, alpha-synuclein was found to be the main component of Lewy bodies by Spillantini, Trojanowski, Goedert and others. ... SNCA gene mutations are important in PD because the protein that gene encodes, alpha-synuclein, is the main component of the ... One mechanism consists of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. This ...
Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of ... alpha-synuclein: can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as ... Alpha-synuclein can damage membranes by inducing membrane curvature,[12] and cause extensive tubulation and vesiculation when ...
"Alpha-synuclein and tau: teammates in neurodegeneration?". Mol Neurodegener. 9: 43. doi:10.1186/1750-1326-9-43. PMC 4230508 . ... Tauopathies are often overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins. ... "Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons". Cell. 154 (1): 103-17. doi:10.1016/j.cell. ...
"Alpha-synuclein and tau: teammates in neurodegeneration?". Mol Neurodegener. doi:10.1186/1750-1326-9-43. PMC 4230508 . PMID ... are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, ... Jun 2015). "α-Synuclein strains cause distinct synucleinopathies after local and systemic administration". Nature. advance ... Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Because each of the ...
Kawahara K, Hashimoto M, Bar-On P, Ho GJ, Crews L, Mizuno H, Rockenstein E, Imam SZ, Masliah E (March 2008). "alpha-Synuclein ... Parkin might promote aggregation of alpha-synuclein and synphilin-1 into Lewy bodies, which are conjugated to Lys63-linked poly ... Another parkin substrate, synphilin-1 (encoded by SNCAIP), is an alpha-synuclein interacting protein that is enriched in the ... Parkin (ligase) has been shown to interact with: Alpha-synuclein, CASK, CUL1, FBXW7 and GPR37, HSPA1A, HSPA8, Multisynthetase ...
Lee FJ, Liu F, Pristupa ZB, Niznik HB (2001). "Direct binding and functional coupling of alpha-synuclein to the dopamine ... Dopamine transporter has been shown to interact with: Alpha-synuclein, PICK1, and TGFB1I1. Apart from these innate protein- ... Wersinger C, Sidhu A (2003). "Attenuation of dopamine transporter activity by alpha-synuclein". Neurosci. Lett. 340 (3): 189-92 ...
Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC (November 2005). "Alpha-synuclein cooperates with CSPalpha in ... 2005). "Characterization of the G alpha(s) regulator cysteine string protein". J. Biol. Chem. 280 (34): 30236-41. doi:10.1074/ ... "The synaptic vesicle protein CSP alpha prevents presynaptic degeneration". Neuron. 42 (2): 237-51. doi:10.1016/S0896-6273(04) ... encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis". American Journal ...
"Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein". The Journal of Biological Chemistry. 275 ( ... Pronin AN, Morris AJ, Surguchov A, Benovic JL (Aug 2000). "Synucleins are a novel class of substrates for G protein-coupled ... Zhou H, Yan F, Tai HH (Sep 2001). "Phosphorylation and desensitization of the human thromboxane receptor-alpha by G protein- ...
... the primary structural component of which is alpha-synuclein. Cortical Lewy bodies are also composed of alpha-synuclein fibrils ... Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM (February 2004). "Aggresomes formed by alpha-synuclein and synphilin- ... A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin, neurofilament protein ... Engelender S (April 2008). "Ubiquitination of alpha-synuclein and autophagy in Parkinson's disease". Autophagy. 4 (3): 372-4. ...
Esteves, AR; Arduíno, DM; Silva, DF; Oliveira, CR; Cardoso, SM (2011). "Mitochondrial Dysfunction: The Road to Alpha-Synuclein ... Parkinson's disease is characterized by inclusions of a protein called alpha-synuclien (Lewy bodies) in affected neurons that ...
... stands for "synuclein, alpha interacting protein" and can be signified by SNCAP_HUMAN, synphilin 1, synuclein, alpha ... "Entrez Gene: SNCAIP synuclein, alpha interacting protein (synphilin)". Neystat M, Rzhetskaya M, Kholodilov N, Burke RE (June ... Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM (2004). "Aggresomes formed by alpha-synuclein and synphilin-1 are ... The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic ...
"Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications". Ann Neurol. 55 (2): 174-9. doi:10.1002/ ...
It inhibits PTK2B/RAFTK activity and regulates alpha-synuclein phosphorylation. It interacts with Signal-regulatory protein ... and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein ... RA receptor alpha in acute promyelocytic leukemia cells". The Journal of Biological Chemistry. 276 (25): 22375-81. doi:10.1074/ ... alpha and directs integrin-activated cytoskeletal reorganization in macrophages. GRCh38: Ensembl release 89: ENSG00000005020 - ...
Esteves, AR; Arduíno, DM; Silva, DF; Oliveira, CR; Cardoso, SM (2011). "Mitochondrial Dysfunction: The Road to Alpha-Synuclein ... Additionally, in the microenvironment of cancer cells, there is an increase in hypoxia-inducible transcription factor 1-alpha ( ...
Chen, M.; Margittai, M.; Chen, J.; Langen, R. (2007). "Investigation of alpha-Synuclein Fibril Structure by Site-directed Spin ... to understand the structure of amyloid fibrils and the structure of membrane bound Parkinson's disease protein alpha-synuclein ...
Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. The main known risk factor is age. ... alpha-synuclein: can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as ... The latest research on pathogenesis of disease has shown that the death of dopaminergic neurons by alpha-synuclein is due to a ...
A study in 2018 suggests a post-translationally modified form of the protein called alpha-synuclein may be a causal agent for ... Arima K, Uéda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (November 1998). "NACP/alpha-synuclein ... Recent studies have shown that the major filamentous component of glial and neuronal cytoplasmic inclusions is alpha-synuclein. ... "Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy". PLoS ONE. 4 (9): e7114. Bibcode ...
Singleton AB (2005). "Altered alpha-synuclein homeostasis causing Parkinson's disease: the potential roles of dardarin". Trends ... "Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein ...
Elkon H, Don J, Melamed E, Ziv I, Shirvan A, Offen D (June 2002). "Mutant and wild-type alpha-synuclein interact with ...
Vallenius T، Luukko K، Mäkelä TP (2000). "CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4 ... binds to alpha-actinin-1 and associates with actin filaments and stress fibers in activated platelets and endothelial cells.". ...
... indicating that alpha-synuclein antagonizes SNARE function. Ykt6 reversed alpha-synuclein inhibition much more effectively than ... Finally, soluble alpha-synuclein A53T directly bound ER/Golgi SNAREs and inhibited SNARE complex assembly, providing a ... Overexpression of wild type or the familial disease-associated A53T mutant alpha-synuclein delayed transport by up to 50%; ... We tested elements of this hypothesis by expressing human alpha-synuclein in mammalian kidney and neuroendocrine cells and ...
Ubiquitin positive, alpha-B-crystallin (synuclein) positive, alpha- and beta-tubulin positive, tau-protein positive ... Ubiquitin positive, alpha-B-crystallin (synuclein) positive, alpha- and beta-tubulin positive, tau-protein positive ... The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol. 2005. 109:129-40. [Medline]. ... GCIs are ubiquitin-positive, tau-positive, and alpha-synuclein ̶ positive oligodendroglial inclusions. They are different from ...
The cause of MSA is unknown, but it seems related to the build-up of a protein (alpha-synuclein) in glial cells that protect ...
The brain cells of a person with multiple system atrophy contain misfolded alpha-synuclein protein (of which there is lots of ... Its thought that a build-up of abnormal alpha-synuclein is responsible for the loss of brain cells. ...
... is a neurodegenerative disease with glial cytoplasmatic inclusion organic structures incorporating alpha synuclein protein. ...
Therefore, NACP is now referred to as human alpha-synuclein. Alpha-synuclein is a synuclein protein of unknown function ... which contain rich cytosolic alpha-synuclein but very low levels of mitochondrial alpha-synuclein. It has been shown that alpha ... The human alpha-synuclein protein is made of 140 amino acids and is encoded by the SNCA gene. An alpha-synuclein fragment, ... Other isoforms are alpha-synuclein-126, which lacks residues 41-54 due to loss of exon 3; and alpha-synuclein-112, which lacks ...
"Cellular milieu imparts distinct pathological {alpha}-synuclein strains in {alpha}-synucleinopathies," by Chao Peng, Ronald J. ... A. "[alpha]-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B," by Diana G Ferreira, ... C. "{alpha}-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation ... "alpha}-Synuclein promotes dilation of the exocytotic fusion pore," by Todd Logan, Jacob Bendor, Chantal Toupin, Kurt Thorn & ...
The behavior of alpha-synuclein in neurons.. Fortin DL1, Nemani VM, Nakamura K, Edwards RH. ... alpha-Synuclein localizes to the nerve terminal, but biochemical experiments have not revealed a tight association with ... To address the dynamics of the protein in live cells, we have used photobleaching and found that alpha-synuclein exhibits high ... In addition to the presumed role of alpha-synuclein dynamics in synaptic function, changes in its physiological behavior may ...
Dominantly inherited mutations in alpha-synuclein cause Parkinsons disease, but the physiological role of alpha-synuclein ... Alpha-synuclein and cysteine-string protein-alpha (CSPalpha) are abundant synaptic vesicle proteins independently linked to ... transgenic alpha-synuclein ameliorates this inhibition. In preventing neurodegeneration in CSPalpha-deficient mice, alpha- ... Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.. Chandra S1, Gallardo G, Fernández-Chacón R, Schlüter ...
... by modulation of glial function following activation by soluble or insoluble modified alpha-synuclein (alpha-syn), a chief ... Nitrated alpha-synuclein-activated microglial profiling for Parkinsons disease.. Reynolds AD1, Glanzer JG, Kadiu I, Ricardo- ... alpha-Syn is nitrated during oxidative stress responses and in its aggregated form, induces inflammatory microglial functions. ... To this end, PD-associated inflammation was modeled by stimulation of microglia with aggregated and nitrated alpha-syn. These ...
The rationale for this project is that a therapeutic antibody against alpha-synuclein will be able to block its harmful effects ... Project Description: Antibodies binding to alpha-synuclein have been selected in cell models. One of them has shown positive ... By antibody engineering we will learn about the importance of the strength of antibody binding to alpha-synuclein, and ... Relevance to Diagnosis/Treatment of Parkinsons Disease: Immunotherapy targeting alpha-synuclein is a new way of treating PD. ...
Rabbit polyclonal Alpha-synuclein antibody validated for ICC/IF and tested in Human and Rat. Referenced in 4 publications. ... Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine ... Synthetic peptide corresponding to Human Alpha-synuclein aa 111-131 (C terminal).. Sequence: GILEDMPVDPDNEAYEMPSEE ... A 6.4 Mb duplication of the a-synuclein locus causing frontotemporal dementia and Parkinsonism: phenotype-genotype correlations ...
Chicken polyclonal Alpha-synuclein antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, Horse, Chicken, Cow, Human ... Protein - Recombinant Human Alpha-synuclein protein aggregate (Active) (ab218819) WB, Functional Studies, SDS-PAGE ... Anti-Alpha-synuclein antibody (ab190376) at 1/2000 dilution + Rat brain crude extract. Predicted band size: 14 kDa. ... Ab190376 staining alpha-synuclein in rat cerebellum tissue sections at 1/3000 dilution (red) and co-stained with rabbit ...
Alpha-synuclein Expression Lowering therapeutics: Hit Confirmation. MJFF Research Grant, 2011. Objective/Rationale:. Simply ... To rid brains of Parkinsons patients of alpha-synuclein toxicity one can attempt to clear the protein from the brain, block ... Brains of most patients with Parkinsons are littered with intracellular accumulations of alpha-synuclein, a small 140 amino- ... or ameliorate the consequences of alpha-synuclein toxicity. We hypothesize, that the most direct and acute solution, however, ...
Total alpha-synuclein concentration in CSF and oligomeric/total alpha-synuclein ratio in CSF [ Time Frame: Day 0 ]. *Oligomeric ... The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies. ... and total alpha-synuclein concentration in plasma and oligomeric/total alpha-synuclein ratio in plasma [ Time Frame: Day 0 ]. ... Oligomeric Alpha-synuclein in Multiple System Atrophy (BIOAMS). The safety and scientific validity of this study is the ...
A major component of these inclusions is phosphorylated alpha-synuclein (,i,α,/i,-SYN) protein. There is evidence that ,i,α,/i ... A major component of these inclusions is phosphorylated alpha-synuclein (α-SYN) protein. There is evidence that α-SYN pathology ... K. M. Shannon, A. Keshavarzian, H. B. Dodiya, S. Jakate, and J. H. Kordower, "Is alpha-synuclein in the colon a biomarker for ... M. G. Cersosimo, C. Perandones, F. E. Micheli et al., "Alpha-synuclein immunoreactivity in minor salivary gland biopsies of ...
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Alpha-synucleinUniRule annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, ... tr,A0A2I3N0Z9,A0A2I3N0Z9_PAPAN Alpha-synuclein OS=Papio anubis OX=9555 GN=SNCA PE=3 SV=1 ... Belongs to the synuclein family.UniRule annotation. Automatic assertion according to rulesi ...
2009) Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem ... Templated seeding of alpha-synuclein aggregation. Marija Iljina, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. ... Templated seeding of alpha-synuclein aggregation. Marija Iljina, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. ... 2008) alpha-Synuclein gene duplication is present in sporadic Parkinson disease. Neurology 70(1):43-49. ...
Blood Plasma of Patients with Parkinsons Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity. Peng Wang,1,2 Xin Li ... This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its ...
2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34:521 ... 2003) Alpha-synuclein pathology affecting Bergmann glia of the cerebellum in patients with alpha-synucleinopathies. Acta ... Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain. Weili Yang, Guohao Wang, Chuan-En Wang, Xiangyu Guo ... Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain. Weili Yang, Guohao Wang, Chuan-En Wang, Xiangyu Guo ...
Alpha-Synuclein Detection. Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult ... Alpha-synuclein (C‑terminus). 18671A, B. IHC. WB. Human. (S122). Rabbit IgG. Cross‑reacts with mouse and rat alpha-synuclein. ... ELISAs for Alpha-Synuclein Detection. The human alpha-synuclein assay kit (Cat. # 27740A) is a solid-phase sandwich ELISA using ... Antibodies for Alpha-Synuclein Detection. Anti-human alpha-synuclein antibody (Cat. # 18671A, B) is an affinity-purified IgG ...
Targeting alpha-synuclein in the gut may slow down Parkinsons disease. Aggregates of the protein alpha-synuclein arising in ... is caused by the buildup of alpha-synuclein proteins in the brain. The biological function of alpha-synuclein is still not ... ... Research by University at Buffalo biologists is providing new insights into alpha-synuclein, a small acidic protein associated ... are associated with the accumulation of alpha-synuclein proteins in the brain. Researchers at the German Center for ...
Invitrogen Anti-alpha Synuclein Recombinant Polyclonal (14HCLC), Catalog # 710110. Tested in Western Blot (WB), ... Mutation of the alpha-synuclein gene is associated with familial forms of PD. Alpha-Synuclein is known to reduce the ... Alpha-Synuclein is involved in the formation of SNARE complexes, and most significantly, aggregated alpha-synuclein is one of ... Alpha-Synuclein belongs to the Synuclein family, which includes beta and gamma Synuclein, and is predominantly expressed in ...
Member of the synuclein family of soluble proteins (alpha-synuclein, beta-synuclein and gamma-synuclein) that are commonly ... Alpha-synuclein. Author: Meenakshi Vij Gupta, M.D. (see Authors page). Revised: 23 May 2016, last major update May 2016. ... Both the sporadic and the familial form of Alzheimer disease also demonstrate alpha-synuclein protein * In recent years, ... several studies have shown that alpha-synuclein aggregation can also be detected outside the central nervous system, ...
  • Toxicity of human alpha-synuclein when expressed in simple organisms can be suppressed by overexpression of endoplasmic reticulum (ER)-to-Golgi transport machinery, suggesting that inhibition of constitutive secretion represents a fundamental cause of the toxicity. (umt.edu)
  • In in vitro reconstitutions, purified alpha-synuclein A53T protein specifically inhibited COPII vesicle docking and fusion at a pre-Golgi step. (umt.edu)
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