alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.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.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.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Reference Standards: A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy.Publications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)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.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.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)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)Neocortex: The largest portion of the CEREBRAL CORTEX in which the NEURONS are arranged in six layers in the mammalian brain: molecular, external granular, external pyramidal, internal granular, internal pyramidal and multiform layers.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.Extrapyramidal Tracts: Uncrossed tracts of motor nerves from the brain to the anterior horns of the spinal cord, involved in reflexes, locomotion, complex movements, and postural control.Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.ArchivesAlzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Dementia, Vascular: An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44)Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous system.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.TexasTherapeutic Misconception: Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.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.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 ProteinsAccess 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.Research Support as Topic: Financial support of research activities.Authorship: The profession of writing. Also the identity of the writer as the creator of a literary production.Software: Sequential operating programs and data which instruct the functioning of a digital computer.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.PrimatesBrain: 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.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.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.Gene Duplication: Processes occurring in various organisms by which new genes are copied. Gene duplication may result in a MULTIGENE FAMILY; supergenes or PSEUDOGENES.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.PhosphoproteinsCentral Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.EuropeInternet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.Europe, Eastern

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)

*Amyloid beta

... as has aggregation of alpha synuclein. While Aβ has been implicated in cancer development, prompting studies on a variety of ... Rekas A, Jankova L, Thorn DC, Cappai R, Carver JA (Dec 2007). "Monitoring the prevention of amyloid fibril formation by alpha- ... "Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner". Journal of ...

*Alpha-synuclein

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 ...

*Alice Lazzarini

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 ...

*Contursi Terme

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 ...

*History of Parkinson's disease

... 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 ...

*Maria Grazia Spillantini

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 ...

*A53T Mutation

"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 ...

*Management of Parkinson's disease

Preclinical research also targets alpha-synuclein. Selegiline is in a group of medications called monoamine oxidase type B (MAO ...

*Parkinson's disease

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 ...

*Tauopathy

"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. ...

*Synucleinopathies

"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 ...

*Parkin (ligase)

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 ...

*Dopamine transporter

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 ...

*DNAJC5

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 ...

*GRK5

"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- ...

*Lewy body

... 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. ...

*Autophagy

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 ...

*SNCAIP

... 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 ...

*William Langston

"Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications". Ann Neurol. 55 (2): 174-9. doi:10.1002/ ...

*SKAP2

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 - ...

*Mitophagy

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 ( ...

*Synuclein

... alpha-synuclein, beta-synuclein, and gamma-synuclein. Interest in the synuclein family began when alpha-synuclein was found to ... Alpha-synuclein InterPro: IPR002460 Beta-synuclein InterPro: IPR002461 Gamma-synuclein InterPro: IPR002462 Normal cellular ... All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid- ... Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally ...

*Site-directed spin labeling

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 ...

*Neurodegeneration

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 ...

*LRRK2

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 ...

*Multiple system atrophy

A study in 2015 suggests a new type of prion from the protein called alpha-synuclein, may be a causal agent for the disease. ... Recent studies have shown that the major filamentous component of glial and neuronal cytoplasmic inclusions is alpha-synuclein ... "Co-localization of alpha-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with ... although research indicates that a prion form of the alpha-synuclein protein may cause the disease. About 55% of MSA cases ...

*Coproporphyrinogen III oxidase

Elkon H, Don J, Melamed E, Ziv I, Shirvan A, Offen D (June 2002). "Mutant and wild-type alpha-synuclein interact with ...
Multiple system atrophy (MSA) is a rare neurodegenerative disorder which is characterized by a variable combination of parkinsonism, cerebellar dysfunction, autonomic failure, and additional signs. No effective treatment is available. Together with PD and Lewy body dementia, MSA belongs to a group of neurodegenerative disorders, the alpha-synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein. The development of biological markers for the diagnosis and prognosis in MSA remains an unmet need. Such biological markers are crucial for future disease-modification and neuroprotection trials. Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature in MSA. The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies.. The study will compare alpha-synuclein levels in CSF and plasma between patients suffering from AMS and controls who are patients ...
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
Recombinant Proteins , α-Synuclein & β-Synuclein , EndoClear * Human Recombinant alpha-Synuclein Protein; Full-length Recombinant human alpha-synuclein (GenBank Accession # NP_000336) was expressed in E. coli., and purified from bacterial lysate using proprietary method. Endotoxin was further removed by proprietary technique. Molecular weight of the recombinant α-synuclein protein is 14.5 kDa. α-Synuclein is a major component of Lewy bodies in the affected neurons in Parkinsons disease. This protein has a mass of 14.5 kDa (140 amino acids long) and consists of a conserved degenerative amino-terminal domain and an acidic carboxyl-terminal with higher sequence divergence. α-Synuclein is predominantly expressed in brain, specifically in cerebellum, thalamus, neocortex, hippocampus, and striatum regions. Other tissues express α-Synuclein at very low levels. The physiological role of α-synuclein is not yet well understood. However, the presence of imperfect KTKEGV lipid interacting
Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, where it is seen mainly in presynaptic terminals. It is predominantly expressed in the neocortex, hippocampus, substantia nigra, thalamus, and cerebellum. It is predominantly a neuronal protein, but can also be found in glial cells. Recent evidence suggests that alpha-synuclein functions as a molecular chaperone in the formation of SNARE complexes. Alpha-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the songbird brain during a period of song-acquisition-related synaptic rearrangement.[1] Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinsons disease, dementia with Lewy bodies, and multiple system atrophy. Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as the non-Abeta ...
Dedmon, M. M., Christodoulou, J., Wilson, M. R. and Dobson, C. (2005). Heat shock protein 70 inhibits alpha-synuclein fibril formation via preferential binding to prefibrillar species. Journal of Biological Chemistry, 280 (15), 14733-14740.. ...
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
Do Mutations in the Alpha-synuclein Gene Cause Dopamine-dependent Oxidative Stress and Neurodegeneration in a Genetic Model of Parkinsons Disease?. The Parkinson Alliance. A non-profit fundraising organization whose sole mission is to raise money for the best Parkinsons Disease researchers doing the most promising research.
Parkinsons Disease (PD) is a debilitating neurodegenerative movement disorder, whose clinical markers include the formation of alpha-Synuclein (alpha-Syn) rich...
Abstract Abnormal folding and accumulation of alpha-synuclein is implicated in several neurological disorders including Parkinsons disease. Although alpha-synuclein is a typical c..
The Oct. 6 study in Neuron by Virginia Lee, PhD, and colleagues, strengthens earlier conclusions from both animal models and human patients suggesting that alpha-synuclein pathology released from dying neurons is transmitted to adjacent cells, which experts say is similar to the spread of misfolded prion protein in Creutzfeldt-Jakob disease. The study also presents a simple new cell-based model of sporadic PD for testing new therapies to stop alpha-synuclein transmission or misfolding.. Dr. Lee, professor of pathology and lab medicine at the University of Pennsylvania School of Medicine in Philadelphia, is hesitant to describe the transmission process as prion-like. While pathology spreads from cell to cell, she said, "there is absolutely no evidence that Parkinson disease can be passed from one person to another. We really dont want to create public fear.". The first strong evidence that PD may spread within the nervous system came in 2003, with careful post-mortem examinations by Heiko Braak, ...
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 ...
Abstract alpha-Synuclein (alphaSyn) can self-associate, forming oligomers, fibrils, and Lewy bodies, the pathological hallmark of Parkinson disease. Current dogma suggests that oli..
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
PBT434 is a novel, orally bioavailable, moderate iron affinity 8-hydroxyquinazolinone which is being developed for treatment of Parkinsonian conditions. We adapted commonly used Parkinsonian toxin models and the hA53T α-synuclein transgenic mouse to investigate the therapeutic potential of PBT434 to slow or prevent progressive neurodegeneration in PD. We found that PBT434 preserved SNpc neuron number in animal models of SNpc degeneration and synucleinopathy which translated to improved motor function accompanied by reduced levels of α-synuclein and a reduction in markers of oxidative stress. The observation that the analog of PBT434, (PBT434-met), in which the metal binding site was blocked, had no protective effect, is consistent with the proposed metal-centric mechanism of action.. Although there is an accumulation of iron in the neurons of the SN in PD [71], it may be simplistic to characterize the condition as a disease of iron overload analogous to hemochromatosis or thalassemia in which ...
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There are no specific protocols for Recombinant Human Alpha-synuclein (mutated A53 T) protein (ab51184). Please download our general protocols booklet
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 ...
Research proven mouse monoclonal alpha Synuclein antibody. alpha Synuclein is primarily located at presynaptic terminals and is found membrane bound in dopaminergic neurons. Useful for the study of Neurodegenerative Diseases inluding Parkinsons and Alzheimers.Excellent IF and WB images in product description.
Cellular senescence (deterioration) is a critical factor of biological aging that occurs in almost all peripheral tissues but little is known about its role in age-related neurodegenerative disorders, such as Parkinsons disease (PD). Senescence occurs in dividing cell types and halts cell proliferation (growth) in an irreversible manner. This process is caused by stress and puts cells at risk for tumor formation. Once established, these cells express a senescence-associated secretory phenotype (SASP), the pro-inflammatory secretion of cytokines and other factors that contribute to the age-related loss of peripheral tissue function. We aim to interrogate induction of senescence and SASP in response to alpha-synuclein (protein clumps) within the most prevalent dividing cell type in the brain, the astrocyte (cells that provide support and clean waste in the brain), and how this in turn affects dopaminergic cell health in relation to PD.. Hypothesis ...
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 ...
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 ...
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 ...
Alpha-synuclein (α-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that α-syn induces fibrillization of tau and that coincubation of tau and α-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of α-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human α-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human α-syn plus P301L mutant tau. This suggests that interactions between α-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases.. ...
Cell loss in Parkinsons and Parkinsons-plus diseases is linked to abnormal, aggregated forms of the cytoplasmic protein, a-synuclein (a-syn). The factors causing a-syn aggregation may include oxidative stress, changes in protein turnover and dysregulation of calcium homeostasis, resulting in cytotoxic aggregated a-syn species. Recently, we showed that raised calcium can promote a-syn aggregation. We have now investigated the effects of raised calcium combined with oxidation/oxidative stress on a-syn aggregation both in vitro and in vivo. We treated monomeric a-syn with calcium, hydrogen peroxide or calcium plus hydrogen peroxide in vitro and used size exclusion chromatography, fluorescence correlation spectroscopy, atomic force microscopy and scanning electron microscopy to investigate protein aggregation. Our in vitro data is consistent with a cooperative interaction between calcium and oxidation resulting in a-syn oligomers. In cell culture experiments, we used thapsigargin or ionophore ...
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.
We will extend a line of investigation that suggests that multiple hits, consisting of mishandling of 1) alphasynuclein (a-syn) degradation, 2)...
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
BioAssay record AID 2471 submitted by Broad Institute: Luminescence Cell-Based Dose-Confimation HTS to Identify Inhibitors of of 5UTR Stem-Loop Driven Alpha-Synuclein mRNA Translation in H4 Neuroglioblastoma Cells.
Paleologou KE, Oueslati A, Shakked G, Rospigliosi CC, Kim HY, Lamberto GR, Fernandez CO, Schmid A, Chegini F, Gai WP, Chiappe D, Moniatte M, Schneider BL, Aebischer P, Eliezer D, Zweckstetter M, Masliah E, Lashuel HA. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions ...
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.
No advice. http://ourparkinsonsplace.blogspot.com contains general information about medical conditions and treatments. The information is not advice, and should not be treated as such. I have copied from organizations the information. This is put together strictly to read and you to talk to your medical doctor about. I search on the internet and copy and share the information on my site. IT IS IMPORTANT TO UNDERSTAND I AM A PERSON WITH PARKINSONS DISEASE. I HAVE NO MEDICAL EDUCATION, I JUST WANT TO SHARE WITH YOU WHAT I READ ON THE INTERNET. IT IS UP TO YOU TO DECIDE WHETHER TO READ IT AND TALK IT OVER WITH YOUR DOCTOR. I AM JUST THE COPIER OF DOCUMENTS FROM THE COMPUTER. I DO NOT HAVE PROOF OF FACT OR FICTION OF THE INFORMATION.. No warranties. The medical informationhttp://ourparkinsonsplace.blogspot.com is provided without any representations or warranties, express or implied.. http://ourparkinsonsplace.blogspot.com makes no representations or warranties in relation to the medical ...
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…
alpha Synuclein Polyclonal Antibody from Invitrogen for Western Blot and Immunoprecipitation applications. This antibody reacts with Human, Mouse, Non-human primate, Rat samples. Supplied as 100 µL purified antibody in 0.01M HEPES with 0.15M NaCl, 100µg/ml BSA, 50% glycerol and no preservative; pH 7.5.
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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。
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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.. ...
Alpha-synuclein is expressed predominantly in the brain, where it is concentrated in presynaptic nerve terminals. The deposition of the abundant
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 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 ...
Bick RJ, Poindexter BJ, Kott MM, Liang YA, Dinh K, Kaur B, Bick DL, Doursout MF, Schiess MC. Cytokines disrupt intracellular patterns of Parkinsons disease-associated proteins alpha-synuclein, tau and ubiquitin in cultured glial cells ...
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 ...
Parkinsons disease (PD) is linked to impaired degradation and accumulation of the misfolded protein, alpha-synuclein. Therefore, accelerating the degradation of alpha-synuclein is of therapeutic interest. Our lab has tested the hypothesis that α-synuclein uses endocytosis as a route to the lysosome for its degradation. We have found evidence that several endocytosis genes regulate α-synucleins PD related properties. Most importantly, the absence of vps28 increases α-synuclein aggregation and cellular accumulation, and confers toxicity in a yeast PD model. I, specifically, found that increasing the concentration of α-synuclein in yeast that lack vps28 further enhances each of these pathological characteristics.
Lee and colleagues found that injecting preformed clumps of human alpha-synuclein into the brains of young mice accelerated disease onset and severity. These clumps seemed to act as "seeds" that recruited even the mouse version of alpha-synuclein into new clumps, which then spread throughout the brain. The pattern of spreading from neuron to neuron suggests that the clumps may hijack the highway traveled by normal brain signals ...
Biogen/Neurimmune: Neurimmune received its Christmas present early this year, but will investors? On Dec. 21 came news the Swiss biotech was selling three preclinical neurodegenerative programs to Biogen Idec for $32.5 million upfront and another $395 million in milestone payments. As part of the deal Biogen takes on responsibility for all further development-and importantly cost-for the compounds, which target the neurotoxic proteins alpha-synuclein, tau, and TDP-43. If Biogen seems enamored with Neurimmunes proprietary Reverse Translational Medicine platform (this is the second time its inked a deal with Neurimmune), its a sure bet the biotechs founders, Karsten Henco and Edward Stuart of HS Life Sciences arent complaining. The two gentlemen staked the company with $6 million nearly four years ago, and havent had to put in another dime, letting the partnerships fund the companys growth. (Now thats capital efficiency.) IN VIVO couldnt determine if Neurimmune will pull a Knopp and return ...
New study results from Austrian biotech AFFiRiS support continued development of its vaccine against the key Parkinsons protein alpha-synuclein.
Many previous studies have explored the protein content of LBs, leading to the identification of ,90 proteins in these intraneuronal inclusions (Wakabayashi et al., 2013). We confirm that many proteins copurify with the detergent-insoluble fraction of synucleinopathy brains (Fig. 3), but early pathogenic changes in protein distribution are likely to be obscured at disease end-stage by proteins that are nonspecifically trapped in degenerating neurons harboring LBs. In this study, we sought to investigate protein pathways disrupted in synucleinopathies by using unbiased proteomic analysis of α-synuclein inclusions in primary hippocampal neurons before the onset of neurodegeneration. Of the large number of proteins detected by LC-MS/MS and subsequently verified by Western blot, only a small number were sequestered in detergent-insoluble aggregates, consistent with an early stage of aggregate formation.. Among the proteins we identified as increased in the insoluble fraction of PFF-treated neurons ...
This project attempts to understand how amyloid proteins cause death of neurones in conditions such as Parkinsons and Alzheimers diseases. By understanding the interaction of monomeric alpha-Synuclein with membranes, I hope to gain insights into which mechanism kills cells in the substantia nigra. Membrane interactions are believed to be crucial in toxic mechanisms, and we employ circular dichroism and fluorescence spectroscopy to monitor binding. Also used is, the increasingly popular, linear dichroism, one major aspect of the project being to improve the reproducability of LD measurements.. ...
AstraZeneca and Takeda Pharmaceutical Company Limited today announced that they have entered an agreement to jointly develop and commercialise MEDI1341, an alpha-synuclein antibody currently in development as a potential treatment for Parkinsons disease (PD). Alpha-synuclein (α-synuclein) is an aggregation-prone protein that contributes to the development of PD.
Mitochonchrion depicted. The breakdown of dopamine produces many reactive oxygen species: molecules containing oxygen with no free electrons. An excess of reactive oxygen species could halt the mitochondrial respiratory cycle. Because of this, dopaminergic neurons may be more susceptible than other neurons to similar levels of mitochondrial dysfunction, which may explain why PD symptoms first arise in dopaminergic areas of the brain.. Many of the genes involved in familial Parkinsons cases are associated with, or affected by, mitochondrial function. For instance, the amount of alpha-synuclein protein, which aggregates to form Lewy bodies and is mutated many familial cases of PD, increases in response to mitochondrial dysfunction under non-disease conditions. This suggests that sporadic cases of PD arise from failure of mitochondrial function (due to environmental factors) and its resulting downstream effects (e.g. protein aggregates). Rotenone, a pesticide similar in structure to MPTP, inhibits ...
We found that all the synuclein molecules could enter the cells where they were localized in both the cytoplasm and nucleus. However, only the wild-type α-syn, which had been shown to have microtubule assembly activity, was able to promote proliferation of the MES23.5 cells. The A53T and A30P mutant α-syn as well as β-syn, which had been proved not to possess microtubule assembly activity, did not exhibit any effect on cell proliferation. Since the α-syn activity in microtubule assembly was shown to be related to its specific functional domain, we then generated different functional fragments (N-terminal 1-65aa, NAC 66-95aa and C-terminal 96-140aa) and tested their activities in cell proliferation. We showed that all the α-syn fragments could enter the cells, but with different subcellular localizations. The N-terminal and NAC fragments were localized in the cytoplasm and the C-terminal fragment mainly in the nucleus. In accordance with the activity for the C-terminal part of α-syn in ...
Clumps of proteins that accumulate in brain cells are a hallmark of neurological diseases such as dementia, Parkinsons disease and Alzheimers disease. Over the past several years, there has been much controversy over the structure of one of those proteins, known as alpha synuclein. MIT computational scientists have now modeled the structure of that protein, most commonly associated with Parkinsons, and found that it can take on either of two proposed structures- floppy or rigid. The findings suggest that forcing the protein to switch to the rigid structure, which does not aggregate, could offer a new way to treat Parkinsons, says Dr. Collin Stultz, an associate professor of electrical engineering and computer science at MIT. "If alpha synuclein can really adopt this ordered structure that does not aggregate, you could imagine a drug-design strategy that stabilizes these ordered structures to prevent them from aggregating," says Dr. Stultz, who is the senior author of a paper describing the ...
Researchers from Brigham and Womens Hospital want to prevent alpha-synuclein from accumulating in the brain. To do so, the team searched for drugs that turn down alpha-synuclein production. They then tested the drugs in mice and stem cells and studied in data from the health records of millions of people living in Norway. The results of their efforts, which point to a new drug development path for PD, are published in Science.
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Understanding the role of the newly identified PARK18 single nucleotide polymorphism in controlling the expression of major compatibility complex II proteins and modulation of Parkinsons disease pathogenesis ...
UAB researchers, led by CAMBAC member David Standaert, M.D., Ph.D., professor and chair of the UAB Department of Neurology, show that a microRNA is involved in early Parkinsons disease pathogenesis. Click here for more. ...
But when the system goes out of balance, the fibrils suppress the normally functioning enzyme, preventing it from fully breaking down the unfolded alpha-synuclein, resulting in even more of the protein being available to form clumps. The clumps also alter the structure of the enzyme in such a way that it produces even more seed fragments. This leads to the formation of more clumps, and so on ...
The D-lab is fascinated by how cells manipulate protein shapes. Our research explores why some proteins cause incurable diseases when they change their normal shape. Cells contain a myriad of proteins that, when in their proper shapes, perform tasks essential for life. Within the intensely crowded environment of cells, most proteins require cooperation of chaperones, which help the proteins fold into proper shapes. If the proteins still misfold, they are targeted for destruction. Sometimes, however, proteins acquire wrong shapes that escape the chaperone assistance and quality control; their buildup can kill cells, especially in the brain, and cause neurological disease. Our goal is to characterize molecular mechanisms and identify proteins that can regulate the toxicity that is linked to alpha-synuclein, the protein that kills nerve cells in Parkinsons disease (PD). Misfolding and aggregation of this protein, oxidative damage, and impairment of protein degradation and protein folding pathways ...
Wang G et al. (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein.. [^] ...
The accumulation of clumps of the protein, alpha-synuclein, in the brain, in is considered to be the hallmark of Parkinsons disease
The invention provides anti-human alpha-synuclein antibodies and methods of using the same.
ウサギ・ポリクローナル抗体 ab51104 交差種: Hu 適用: WB,ELISA,IHC-P…Alpha-synuclein抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
We study mechanisms of neurodegeneration underlying Parkinsons disease and related disorders. Dominant mutations in the alpha-synuclein gene cause a rare familial form of Parkinsons disease. In both familial and sporadic forms of Parkinsons disease, misfolded alpha-synuclein protein accumulates in neuronal inclusions referred to as Lewy bodies and Lewy neurites, indicating that pathways involving alpha-synuclein misfolding are important for pathogenesis. Our recent findings link the accumulation of misfolded alpha-synuclein to mutations in another gene, by demonstrating that disorders caused by mutations in the PLA2G6 gene are also defined by Lewy bodies and Lewy neurites in many of the same neuronal populations affected by Parkinsons disease. PLA2G6 mutations are responsible for a spectrum of hereditary disorders classified as Neurodegeneration with brain iron accumulation (NBIA), infantile neuroaxonal dystrophy (INAD), and parkinsonism-dystonia.. The PLA2G6 gene encodes the A2 ...
α-synuclein is a small protein of 140 amino acids that is highly expressed in the brain. Its function remains poorly understood.10 Synucleinopathies are a group of neurodegenerative diseases associated with the abnormal accumulation of α-synuclein within cytoplasmic inclusions in neurons or oligodendroglia. These α-synuclein containing cytoplasmic aggregates occur throughout the brain, producing cell death and specific motor, autonomic and cognitive dysfunction in four phenotypically distinct synucleinopathies. When α-synuclein deposition occurs in neurons it aggregates into Lewy bodies, producing Parkinson disease (PD), dementia with Lewy bodies (DLB) or pure autonomic failure (PAF). Whereas in multiple system atrophy (MSA) neuronal death probably occurs as a consequence of α-synuclein aggregation in oligodendroglia.. A characteristic feature of the synucleinopathies is that they can all begin with varying degrees of autonomic dysfunction as the sole clinical feature - implying an initial ...
0006] While the molecular bases for PD have not been fully elucidated, several genetic regions have been found to be associated with PD. The PARK1 region at 4q21 contains the alpha-synuclein (SNCA) gene. Certain mutations in this gene confer a rare autosomal dominant form of PD (Duvoisin, R. C. (1996), Recent advances in the genetics of Parkinsons disease, Adv Neurol 69:33-40; Polymeropoulos et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinsons disease, Science 276:2045-7; and Kruger et al. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinsons disease, Nat Genet 18:106-108). The PARK2 region at 6q25-27 contains the parkin gene. The loss of function of both copies of the parkin gene confers an autosomal recessive juvenile form of PD (Abbas et al. (1999) A wide variety of mutation in the parkin gene are responsible for autosomal recessive parkinsonism in Europe, Hum Mol Genet 8:567-574; Lucking et al. (1998) Homozygous deletions in the ...
Ideally, we need a biomarker for PD that changes over time," said Caroline M. Tanner, MD, PhD, director of clinical research at the Parkinsons Institute in Sunnyvale, CA. But, "we have to validate our biomarkers," cautioned Steven Finkbeiner, MD, PhD, associate director and senior investigator at the Gladstone Institute of Neurological Disease at the University of California San Francisco.. Another recommendation supported the development of novel and specific alpha-synuclein PET imaging agents and assays to measure the alpha-synuclein burden in both animal models and human tissue.. Several conference participants made the analogy between alpha-synuclein as a pathological hallmark of PD and amyloid-beta as a signature pathology of Alzheimers disease, stressing the need for alpha-synuclein tracers. The draft document noted that PET imaging is well suited for detecting alpha-synuclein in the living brain using a suitable PET ligand. (NINDS has a Parkinsons Disease Biomarkers Program aimed at ...
Summary Global Markets Directs, Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) - Pipeline Review, H2 2016, provides in depth analysis on Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) targeted pipeline therapeutics. The report provides comprehensive information
Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symptoms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinsons disease (PD). Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amout of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein ...
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Although the pathogenesis of Parkinsons disease (PD) is considered multifactorial, evidence from genetics and cell biology has implicated specific molecular pathways. This article summarizes evidence that suggests that the level of intracellular alpha-synuclein is critical for the onset of neurodegeneration with Lewy bodies and dependent, to a large extent, on lysosomal degradation. The function of other key proteins that emerged from genetics is discussed: Pink1 and Parkin regulate the degradation of damaged mitochondria by the lysosome (mitophagy). Glucocerebrosidase and ATP13A2 are important components of this degradative organelle. VPS35 and LRRK2 may regulate trafficking within lysosome-dependent pathways, such as autophagy and endosomal vesicle recycling. Clinically, diffuse alpha-synucleinopathy or dementia seems to correlate with mutations which interfere with the broader function of lysosomal pathways, whereas a predominantly motor syndrome and nigrostriatal degeneration is associated with
To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing ...
α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinsons disease and multiple system atrophy? Acta Neuropathologica February 2013 (epub) Aoife P. Kiely, Yasmine T Asi, Eleanna Kara, Patricia Limousin, Helen Ling, Patrick Lewis, Christos Proukakis,Niall Quinn, Andrew J. Lees, John Hardy, Tamas Revesz, Henry Houlden and Janice L. Holton a-Synucleinopathies share the common feature…
Parkinson Disease, facts of Parkinson Disease, Symptoms of Parkinson Disease, Risk Factors in Parkinson Disease, Diagnosis of Parkinson Disease, Medical Treatment for Parkinson Disease, Medication of Parkinson Disease, Surgery in Parkinson Disease, Complementary Treatments in Parkinson Disease
Alpha synuclein (αSyn) still remains a mysterious protein even two decades after SNCA encoding it was identified as the first causative gene of familial Parkinsons disease (PD). Accumulation of αSyn causes α-synucleinopathies including PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent advances in therapeutic approaches offer new antibody-, vaccine-, antisense-oligonucleotide- and small molecule-based options to reduce αSyn protein levels and aggregates in patients brain. Gathering research information of other neurological disease particularly Alzheimers disease, recent disappointment of an experimental amyloid plaques busting antibody in clinical trials underscores the difficulty of treating people who show even mild dementia as damage in their brain may already be too extensive ...
E-mail: [email protected] This information is information that BioArctic AB (publ) is obliged to disclose pursuant to the EU Market Abuse Regulation. The information was released for public disclosure, through the agency of the contact persons above, on October 13, 2017, at 10.15 a.m. CET.. About BAN0805. BioArctics product candidate BAN0805 is a monoclonal antibody that selectively binds and eliminates oligomers and protofibrils of alpha-synuclein. BAN0805 aims to halt or slow down the progression of the disease in Parkinson patients. In preclinical studies, BAN0805 has been shown to decrease the levels of alpha-synuclein protofibrils, decrease motor symptoms and double the life span of transgenic Parkinson mice.1). The treatments for Parkinsons disease that are currently on the market are focused on relieving the motor symptoms in Parkinsons patients. BAN0805 has the potential to become one of the first disease modifying treatments for Parkinsons disease.. About ...
GRAND RAPIDS, Mich. (Aug. 8, 2016)-Theyre two of the biggest mysteries in Parkinsons disease research-where does the disease start? And how can it be stopped early in the process?. Now, a new laboratory model of Parkinsons is giving scientists an inside look at what happens in the brain years before motor symptoms appear. Specifically, it demonstrates how abnormal alpha-synuclein proteins, which are strongly associated with Parkinsons, gradually spread from an area of the brain implicated in the early stages of the disease to other regions of the brain ultimately damaged by the disease. The findings were published today in the Journal of Experimental Medicine.. Parkinsons is primarily a disease of aging, with most cases diagnosed after age 60. By the time symptoms appear, more than half of the brain cells that produce dopamine, a chemical messenger needed for voluntary movement, have died. What triggers this process is unknown, although evidence points to a combination of genetic, ...
Parkinsons disease (PD) is a common and incurable neurodegenerative disorder. Loss of midbrain dopaminergic neurons (mDA) of the substantia nigra is the key pathological event in this disorder, but why this cell loss occurs remains a mystery. Much progress has been made by studying genes mutated in inherited forms of PD, thereby identifying cell pathways that might contribute to neuronal death (Hardy, 2010). One such gene is SNCA which encodes α-synuclein. Point mutations and multiplications of SNCA cause familial PD, and variation at this locus is linked with the common sporadic form of the disease. Furthermore, α-synuclein protein is the main component of Lewy bodies: cytoplasmic inclusions seen in mDA neurons that define the disease pathologically. Thus, α-synuclein appears to play a central role in PD pathogenesis. However, studying how it exerts its toxicity has been hampered by the inaccessibility of diseased neurons from patients with the condition, and cell culture systems and ...
Parkinsons disease (PD) is the second most common neurodegenerative disorder, affecting approximately 1% of the population over the age of 65. Around 5% of these cases can be linked to mutations in known genes, one of which is the PINK1 gene, first linked to PD a decade ago. Since then, over 30 mutations in PINK have been described. The PINK1 gene encodes an unusual serine/threonine protein kinase; uniquely among protein kinases, PINK1 is anchored to the mitochondria and furthermore possesses three unusual insertions of unknown function in the N-lobe of its kinase domain. Recently, two important PINK1 substrates have been identified - the ubiquitin E3 ligase Parkin and ubiquitin itself. Phosphorylation of both of these substrates has further been shown to be necessary for the activation of Parkin E3 ligase activity. At the start of this project, little was known about the catalytic properties of PINK1 or the effects of the identified PD- linked mutations due to the lack of a robust in vitro ...
First author Adamantios Mamais tells us about his recent publication in Neurobiology of Disease: At the Queen Square Brain Bank (part of the UCL Institute of Neurology) we hold a large collection of post-mortem human brain tissue from patients with neurodegenerative diseases including Parkinsons disease (PD); a debilitating neurological disorder that affects the central nervous…
Parkinsons disease is a common neurodegenerative disorder and the Dawson lab is studying the genetic basis of PD by investigating the mechanisms by which mutations in familial-linked genes cause PD, with hopes of identifying potential therapeutic targets for developing PD treatments. Current projects include the study of alpha-synuclein, LRRK2, parkin and PINK1.. Nitric oxide is a major player in neuronal cell death and the Dawson team has discovered parthanatos, a caspase-independent programmed cell death pathway involving apoptosis inducing factor (AIF) downstream of NO and its major target poly (ADP-ribose) polymerase (PARP). The team now is further characterizing that pathway to identify targets of AIF and the roles of other cell death effectors with the hope of identifying new signaling pathways that might be amenable to therapeutic intervention. In addition they are investigating the role of poly (ADP-ribose) as signaling molecule.. Representative Publications:. ...
Read about how ProMIS Neurosciences has identified several antibody candidates that target the toxic forms of alpha-synucle in Parkinsons disease.
A common misconception is that Alzheimers disease and dementia are the same thing. Alzheimers disease is simply one form of dementia. Researchers from Texas A&M describe how Alzheimers and other forms of dementia impact the lives of both patients and their families, and provide new insights into minimizing the risks of developing neurodegenerative conditions.... Read More... ...
Lesions known as Lewy bodies (LBs) and Lewy neurites (LNs) characterise brains of Parkinsons disease (PD) patients. Intracellular aggregation of a-synuclein (a-syn) appears to play a key role in the generation of LBs andLNs. Such aggregation in the presence of redox metals may initiate Fenton reaction-mediated generation of reactive oxygen species (ROS). ROS thus generated may result in cytotoxic mechanisms such as the induction of DNA single-strand breaks.. ...
Lewy body diseases, like Parkinsons disease and dementia with Lewy bodies, are characterized by the presence of Lewy bodies (deposits of a misfolded but naturally-occurring protein called alpha-synuclein), and a depletion of the neurotransmitter (chemical messenger) dopamine. The majority of dopamine-producing cells die before motor symptoms of Parkinsons disease emerge. But until now, research has not demonstrated whether the presence of Lewy bodies is linked to the cascade of symptoms in Parkinsons.. The first hints of cell-to-cell transmission of Lewy body pathology came in 2008. Researchers transplanted fetal nerve tissue into the brains of individuals with Parkinsons disease and years later discovered the transplanted cells developed the same pathology. Subsequent research demonstrated that this cell to cell transmission led to cell death. But questions remained as to how Lewy body pathology caused the progressive devastation of Parkinsons disease.. Researchers at the University of ...
Research suggests that alpha-synuclein (SNCA) and NACP-Rep1, a polymorphic complex microsatellite repeat ~10 kb upstream of the SNCA gene translational start, may be involved in substance-use behaviors and craving. This study was the first to examine the effects of diacetylmorphine (DAM) on peripheral SNCA protein expression along with craving in opiate-dependent patients and to compare their NACP-Rep1 allele lengths with those of healthy controls. Using an experimental design, opiate-dependent patients on injectable heroin maintenance were investigated at four time points, twice pre- and post-injection of DAM. SNCA protein levels of 30 DAM-maintained patients were measured using enzyme-linked immunosorbent assay. Participant-rated effects were assessed in 42 patients by Tiffanys Heroin Craving Questionnaire (HCQ), Gossops Short Opiate Withdrawal Scale and Visual Analogs. NACP-Rep1 alleles of 42 patients and 101 controls were analyzed. One-way repeated-measures ANOVAs provided significant ...
Recombinant Proteins , α-Synuclein & β-Synuclein , Recombinant Human β-Synuclein (1-134); The sequence (Accession # NP_003076)) corresponding to the human β-synuclein along with a 6x His tag was expressed in E. coli. Endotoxin (EU/μg): Less than 1 EU per 1 μg of the protein as determined by Limulus Amebocyte Lysate (LAL) quantitative kinetic assay. Beta-synuclein belongs to the family of highly conservative proteins in vertebrates. N-terminal of β-synuclein is highly homologous to α-, γ-synucleins and consists of degenerative KTKEGV repeats (1-4). Similar to α-synuclein, beta-synuclein is found primarily in the brain; however, it does not associate with Lewy bodies in Parkinson disease like α-synuclein (1-4). Beta-synuclein was found to inhibit production of phosphatidic acid by the phospholipase D2 transmembrane protein in vitro (1). In addition, beta-synuclein was detected in many breast and ovarian tumors (4). Recent investigations demonstrated that beta-synuclein can induce
TY - JOUR. T1 - Uric acid as a potential disease modifier in patients with multiple system atrophy. AU - Lee, Ji E.. AU - Song, Sook K.. AU - Sohn, Young H.. AU - Lee, Phil Hyu. PY - 2011/7/1. Y1 - 2011/7/1. N2 - Background: Recent studies have suggested that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of multiple system atrophy. Methods: We evaluated the influence of serum uric acid levels on disease progression in 52 patients with multiple system atrophy using changes in the annualized Unified Multiple System Atrophy Rating Scale scores. Results: The mean annualized Unified Multiple System Atrophy Rating Scale changes were significantly lower in patients with the highest uric acid quartile compared with those with the lowest quartile (8.4 ± 5.1 vs 20.2 ± 16.0, P = .038). Serum uric acid levels had a significant negative correlation with the annualized Unified Multiple System Atrophy Rating Scale changes (r = -0.40, P = .004). Multiple linear regression ...
Ubiquitinated cytoplasmic inclusions are a characteristic feature of the neuronal pathology of neurodegenerative diseases. Immunocytochemical techniques have identified intermediate filaments associated with ubiquitin-immunoreactive inclusions in Alzheimers disease (AD), Parkinsons disease (PD), and Picks disease; however, no core protein has been detected in the ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS). The pathogenesis of these inclusions is not known but the inclusion may result from an accumulation of an abnormal proteins. Here we report a novel protein of 32.5 kDa detected by polyacrylamide gel electrophoresis in the spinal cord in ALS patients. A polyclonal antibody raised against this protein and used for Western blotting, suggests that the novel protein is related to actin. Immunocytochemical studies using this antibody indicate that the protein is found in Lewy body-like inclusions in anterior horn cells of ALS, and in Lewy bodies in the substantia nigra in ...
OBJECTIVE--To further elucidate the relation between diffuse Lewy body disease and Parkinsons disease. METHODS AND RESULTS--The clinical features of nine cases of pure diffuse Lewy body disease without pathological evidence of coexisting Alzheimers neuritic pathology were reported. All patients were aged less than 70 years at onset (mean 62 years). Five patients presented with clinical features, which included assymetric resting tremor had levodopa responsiveness, which were initially indistinguishable from idiopathic Parkinsons disease. All five patients later became demented (mean of three years after presentation). Two further patients presented with parkinsonism and dementia and two patients presented with dementia and developed parkinsonism at a later stage. Hallucinations appeared 2.5-9 years after the onset of symptoms in six patients and were a presenting feature in one patient. All patients met the pathological criteria of idiopathic Parkinsons disease, with respect to the midbrain ...
Epidemiologic studies suggest that occupational exposure to pesticides might increase Parkinson disease risk. Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of α-synuclein, a protein critically involved in Parkinson disease. Therefore, we assessed total blood cell α-synuclein in 90 specimens from 63 agricultural pesticide handlers, mainly Hispanic men from central Washington State, who participated in the state's cholinesterase monitoring program in 2007-2010. Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether α-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. There was no evidence by any of those indicators that exposure to chlorpyrifos was associated with greater blood α-synuclein. We observed somewhat greater ...
Looking for online definition of Lewy body dementia in the Medical Dictionary? Lewy body dementia explanation free. What is Lewy body dementia? Meaning of Lewy body dementia medical term. What does Lewy body dementia mean?

Multiple system atrophy - Genetics Home Reference - NIHMultiple system atrophy - Genetics Home Reference - NIH

The SNCA gene provides instructions for making a protein called alpha-synuclein, which is abundant in normal brain cells but ... In all cases, multiple system atrophy is characterized by clumps of abnormal alpha-synuclein protein that, for unknown reasons ... Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS One. 2009 Sep 22;4(9):e7114 ...
more infohttps://ghr.nlm.nih.gov/condition/multiple-system-atrophy

Anti-Alpha-synuclein antibody (ab15530) | AbcamAnti-Alpha-synuclein antibody (ab15530) | Abcam

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 ...
more infohttp://www.abcam.com/alpha-synuclein-antibody-ab15530.html

Anti-Alpha-synuclein antibody (ab190376) | AbcamAnti-Alpha-synuclein antibody (ab190376) | Abcam

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 ...
more infohttps://www.abcam.com/alpha-synuclein-antibody-ab190376.html

Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.  - PubMed - NCBIAlpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. - PubMed - NCBI

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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/16269331?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1

Medical Xpress - alpha synucleinMedical Xpress - alpha synuclein

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 ...
more infohttps://medicalxpress.com/tags/alpha+synuclein/

Pathology Outlines - Alpha-synucleinPathology Outlines - Alpha-synuclein

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, ...
more infohttp://pathologyoutlines.com/topic/stainsalphasynuclein.html

alpha-Synuclein
     Summary Report | CureHunteralpha-Synuclein Summary Report | CureHunter

A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection. ... alpha-Synuclein. Subscribe to New Research on alpha-Synuclein A synuclein that is a major component of LEWY BODIES that plays a ... 07/19/2002 - "This cell system of oligodendroglial alpha-synuclein expression is a useful system to study alpha-synuclein ... "The study suggests that reduced levels of CSF alpha-synuclein in DLB may reflect the accumulation of alpha-synuclein with Lewy ...
more infohttp://www.curehunter.com/public/keywordSummaryD051844-alpha-Synuclein.do

Alpha-Synuclein Detection: ELISAs and AntibodiesAlpha-Synuclein Detection: ELISAs and Antibodies

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 ...
more infohttp://www.clontech.com/US/Products/Cell_Biology_and_Epigenetics/Brain_and_CNS/Alpha-Synuclein?sitex=10020:22372:US&PEBCL1=7l5uwvG92P7mvnVVdfRJ5R3C3C&PEBCL1_pses=ZGE118626BB0E9861AA82736AC8AEF11AD56B05A5E18CCD6B4F2964846C4D03CBA7757FC0FA1326F25330AC51CAA304C3DDED0D21C7C0DBF1A

Alpha-Synuclein Detection: ELISAs and AntibodiesAlpha-Synuclein Detection: ELISAs and Antibodies

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 ...
more infohttp://www.clontech.com/US/Products/Cell_Biology_and_Epigenetics/Brain_and_CNS/Alpha-Synuclein?sitex=10020:22372:US&PEBCL1=aIKusEIpMwYNK8PQyziG8j4QA5&PEBCL1_pses=ZG3F033B7EEC18F9BA45073BF6903C4F1EEB6153911982C0A4219ACD3AC5CFBF137D0B0BDF9283B8C1884D5D8BD7C9C2FC5238FCDA483F9B63

Nitrated alpha-synuclein-activated microglial profiling for Parkinsons disease.  - PubMed - NCBINitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. - PubMed - NCBI

... 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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/18036154

alpha-synuclein Archives - Neuroscience Newsalpha-synuclein Archives - Neuroscience News

T cells may be tricked into thinking dopamine neurons are foreign due to the build up of damaged alpha-synuclein, a new study ... Researchers detail the complex interaction between alpha synuclein and the prion protein PrPc.... Read More... ... The drug, nortiptyline, has been shown to stop the growth of alpha synuclein.... Read More... ... The Nature study reports four genetic variations are associated with T cell reactivity to alpha synuclein. More than 50% of ...
more infohttp://neurosciencenews.com/neuroscience-terms/alpha-synuclein/

alpha-Synuclein Antibody Sampler Kitalpha-Synuclein Antibody Sampler Kit

Anti-α-Synuclein, 80-96: 2.0 - 10.0 µg/ml. Anti-α-Synuclein (C-Terminal Truncated x-122): 2.0 - 10.0 µg/ml. Anti-α-Synuclein ... Lane 1: 50 ng of recombinant human α-synuclein; Lane 2: 50 ng of recombinant human pS87 α-synuclein; Lane 3: 25 µg of normal ... Lane 1: 50 ng of recombinant human α-synuclein; Lane 2: 50 ng of recombinant C-terminally truncated human α-synuclein (1-122). ... IHC staining of α-synuclein deposits with purified anti-α-Synuclein, C-Terminal Truncated antibody (clone A15127A) on formalin- ...
more infohttps://www.biolegend.com/fr-ch/products/alpha-synuclein-antibody-sampler-kit-15846

Alpha-synuclein Expression Lowering therapeutics: Hit Confirmation | Parkinsons DiseaseAlpha-synuclein Expression Lowering therapeutics: Hit Confirmation | Parkinson's Disease

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, ...
more infohttps://www.michaeljfox.org/foundation/grant-detail.php?grant_id=983

Alpha-Synuclein A53T Knock-in RatAlpha-Synuclein A53T Knock-in Rat

The resulting model expresses a humanized A53T alpha-synuclein protein without endogenous rat alpha-synuclein. This model was ... Youre reviewing: Alpha-Synuclein A53T SNCA Knock-in Rat How do you rate this product? *. 1 1 star ... making this model useful for understanding alpha-synuclein biology and PD pathogenesis.. Download our review of Animal Models ... Alpha-Synuclein A53T SNCA Knock-in Rat TGRL10220 Animal Model. Alpha-Synuclein A53T KI ...
more infohttps://www.horizondiscovery.com/alpha-synuclein-a53t-knock-in-rat

SNCA - Alpha-synuclein - Papio anubis (Olive baboon) - SNCA gene & proteinSNCA - Alpha-synuclein - Papio anubis (Olive baboon) - SNCA gene & protein

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 ...
more infohttps://www.uniprot.org/uniprot/A0A2I3N0Z9

Saliva Alpha-synuclein Levels in LRRK2 Mutation Carriers | Parkinsons DiseaseSaliva Alpha-synuclein Levels in LRRK2 Mutation Carriers | Parkinson's Disease

Saliva Alpha-synuclein Levels in LRRK2 Mutation Carriers. Research Grant, 2014. Study Rationale: Biomarkers are needed to ... Decreased levels of alpha-synuclein in cerebrospinal fluid is the most consistent biological marker of PD to date; however, ... We will measure and compare alpha-synuclein levels in the saliva of LRRK2 mutation carriers who do not have any PD symptoms ( ... Human salivary alpha-synuclein could be a reliable, inexpensive, easily accessible biomarker to 1) assist with early PD ...
more infohttps://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1429

Oligomeric Alpha-synuclein in Multiple System Atrophy - Full Text View - ClinicalTrials.govOligomeric Alpha-synuclein in Multiple System Atrophy - Full Text View - ClinicalTrials.gov

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 ...
more infohttps://clinicaltrials.gov/ct2/show/NCT01485549?cond=%22Multiple+system+atrophy%22&rank=8

Alpha-synuclein transfers from neurons to oligodendrocytes.Alpha-synuclein transfers from neurons to oligodendrocytes.

... Reyes, Juan F LU ; Rey, Nolwen LU ; Bousset, Luc; Melki, Ronald; ... The origin of α-synuclein (α-syn)-positive glial cytoplasmic inclusions found in oligodendrocytes in multiple system atrophy ( ... The origin of α-synuclein (α-syn)-positive glial cytoplasmic inclusions found in oligodendrocytes in multiple system atrophy ( ... article{dce8851e-e03f-4e93-90bb-913db60219ed, abstract = {The origin of α-synuclein (α-syn)-positive glial cytoplasmic ...
more infohttps://lup.lub.lu.se/search/publication/4292243

SNCA / Alpha-Synuclein - LSBioSNCA / Alpha-Synuclein - LSBio

SNCA / Alpha-Synuclein. synuclein, alpha (non A4 component of amyloid precursor). Alpha-synuclein is a member of the synuclein ... synuclein, alpha (non A4 component of amyloid precursor). Synonyms:. SNCA, Alpha-synuclein, PARK4, PD1, Synuclein alpha-140, ... Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may ... Rabbit Polyclonal (IgG) to Human SNCA / Alpha-Synuclein Reactivity:. Rabbit, Mouse, Dog, Bovine, Rat, Pig, Horse, Human, Monkey ...
more infohttps://www.lsbio.com/targets/snca-alpha-synuclein/g409?prefix=a

anti-alpha Synuclein antibody [4D6]  | GeneTexanti-alpha Synuclein antibody [4D6] | GeneTex

... synuclein, alpha (non A4 component of amyloid precursor)) for ELISA, IHC, IHC-Fr, IHC-P, WB. Anti-alpha Synuclein mAb (GTX21903 ... synuclein, alpha (non A4 component of amyloid precursor). Background. The implication of alpha synuclein in neurodegenerative ... The synuclein family includes alpha and beta synucleins and loosely related gamma synuclein and synoretin. The expression is ... alpha synuclein, ubiquitin and associated enzymes. The synuclein phosphoproteins (15-20 kD) are small highly conserved proteins ...
more infohttp://www.genetex.com/alpha-Synuclein-antibody-4D6-GTX21903.html

TSRI - News & View, Scientists Watch as Individual Alpha-Synuclein Proteins Change ShapeTSRI - News & View, Scientists 'Watch' as Individual Alpha-Synuclein Proteins Change Shape

To comply with the National Institutes of Health (NIH) Public Access Policy, a PubMed Central reference number (PMCID) is required in NIH grant applications, proposals, and progress reports for any paper "authored by you or [arising] from your NIH funds (even if you are not an author)" (see http://publicaccess.nih.gov/FAQ.htm#c8).. One way to find the PMCID number is to use PubMed Centrals PMID: PMCID Converter available at http://www.ncbi.nlm.nih.gov/sites/pmctopmid. If you already have the PMID from a PubMed search (it may appear as the Accession Number in your EndNote library), the above converter will provide you with the corresponding PMCID to include in your grant. If you do not have the PMID number, you can look up a PMCID in PubMed. It will be listed in the lower right corner of the AbstractPlus view. A PMCID number will be assigned as soon as an article has successfully been submitted to PMC (see http://publicaccess.nih.gov/FAQ.htm#c9). If you have questions about the NIH Public Access ...
more infohttp://www.scripps.edu/newsandviews/e_20090323/updates.html

Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain | Journal of NeuroscienceMutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain | Journal of Neuroscience

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 ...
more infohttp://www.jneurosci.org/content/35/21/8345

Blood Plasma of Patients with Parkinsons Disease Increases Alpha-Synuclein Aggregation and NeurotoxicityBlood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

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 ...
more infohttps://www.hindawi.com/journals/pd/2016/7596482/abs/

Alpha-synuclein - WikipediaAlpha-synuclein - Wikipedia

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 ...
more infohttps://en.wikipedia.org/wiki/Alpha-synuclein

anti-alpha Synuclein (phospho Ser129) antibody  | GeneTexanti-alpha Synuclein (phospho Ser129) antibody | GeneTex

... synuclein, alpha (non A4 component of amyloid precursor)) for ICC/IF, IHC-P, WB. Anti-alpha Synuclein (phospho Ser129) pAb ( ... synuclein, alpha (non A4 component of amyloid precursor). Background. Alpha-synuclein is a member of the synuclein family, ... which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein ... Storage Conditions: alpha Synuclein (phospho Ser129) antibody. Storage Buffer. Liquid in 0.42% Potassium phosphate, 0.87% ...
more infohttp://www.genetex.com/alpha-Synuclein-phospho-Ser129-antibody-GTX54991.html
  • Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications. (lsbio.com)
  • Certain missense mutations in the alpha synuclein gene (A53T, A30P) have been linked to the familial Parkinsonis disease (PD). (genetex.com)
  • Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. (jneurosci.org)
  • This has been attributed to the spread of α -synuclein ( α -syn) aggregates, which involves release of α -syn from a neuron and its reuptake by a neighboring neuron. (hindawi.com)
  • Here, we determine the concentrations and numbers of aggregates necessary for the effective seeding of alpha-synuclein, thus providing a quantitative framework to understand the conditions when its seeded propagation is favorable. (pnas.org)
  • The origin of α-synuclein (α-syn)-positive glial cytoplasmic inclusions found in oligodendrocytes in multiple system atrophy (MSA) is enigmatic, given the fact that oligodendrocytes do not express α-syn mRNA. (lu.se)
  • The Nature study reports four genetic variations are associated with T cell reactivity to alpha synuclein. (neurosciencenews.com)
  • Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. (lsbio.com)
  • Mab 5G4 recognizes α-sheets of amino acids 47-53 of alpa-Synuclein that is described as amyloidogenic rea-gion and pathologic related structure for detection of synucleopathies (Kovacs 2012). (analytik-jena.de)
  • Mab 10D2 binds to amino acids 118-125 within c-terminal part of the protein and is very suitable for detection of all alpha-Synuclein forms in different applications. (analytik-jena.de)
  • One possible explanation is that UPDRS reflects primarily deficits arising from nigrostriatal degeneration, whereas CSF alpha-synuclein levels are influenced by the whole brain and may serve as a proxy for total brain pathology," says Dr. Zhang. (eurekalert.org)
  • Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. (nih.gov)
  • In preventing neurodegeneration in CSPalpha-deficient mice, alpha-synuclein does not simply substitute for CSPalpha but acts by a downstream mechanism that requires phospholipid binding by alpha-synuclein. (nih.gov)
  • Therefore, the Zhang lab investigated alpha-synuclein in a more readily accessible body fluid (saliva) and found that levels tended to be lower in PD patients compared to control subjects and possibly decreased as the severity of motor symptoms increased. (michaeljfox.org)
  • The finding that alpha-synuclein levels decrease as PD progresses, yet those with higher alpha-synuclein levels experience faster cognitive decline, is somewhat counterintuitive," comments Dr. Zhang. (eurekalert.org)
  • Pujols J, Peña-Díaz S, Conde-Giménez M, Pinheiro F, Navarro S, Sancho J, Ventura S. High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors. (mdpi.com)
  • alpha-Syn is nitrated during oxidative stress responses and in its aggregated form, induces inflammatory microglial functions. (nih.gov)
  • We wish to determine (i) if saliva alpha-synuclein levels are already decreased in subjects who currently do not have any clinical symptoms but who may go on to develop PD, and (ii) if saliva alpha-synuclein levels decrease further once clinical symptoms appear and the disease progresses. (michaeljfox.org)
  • The human alpha-synuclein assay kit (Cat. (clontech.com)
  • Alpha-synuclein is a protein that is abundant in the human brain. (wikipedia.org)
  • Human salivary alpha-synuclein could be a reliable, inexpensive, easily accessible biomarker to 1) assist with early PD diagnosis when treatment could be most effective, 2) predict/follow PD progression, and 3) evaluate the efficacy of existing and future neuroprotective treatments. (michaeljfox.org)
  • I treated differentiated human neuroblastoma SY5Y cell culture expressing a Alpha-Syn-GFP fusion with the 21 most commonly used pesticides in Florida?s orange industry for 24 hrs. (ufl.edu)