A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
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.
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.
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.
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.
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)
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
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.
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.
A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The 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.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
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.
One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.
Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.
An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.
An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.
This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.
Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.
A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.
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).
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 produced by a single clone of cells.
Immunoglobulins produced in response to VIRAL ANTIGENS.
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.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Proteolytic breakdown of the MITOCHONDRIA.
Neurological condition characterized by disturbances in VISUAL PERCEPTION, most often of BODY SCHEMA, TIME PERCEPTION and HALLUCINATIONS. It is associated with MIGRAINE, infections (e.g., INFECTIOUS MONONUCLEOSIS), FEVER, EPILEPSY, and other neurological and psychiatric disorders.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Time period from 1901 through 2000 of the common era.
Individual's rights to obtain and use information collected or generated by others.
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.
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.
Detailed account or statement or formal record of data resulting from empirical inquiry.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Processes occurring in various organisms by which new genes are copied. Gene duplication may result in a MULTIGENE FAMILY; supergenes or PSEUDOGENES.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Toxicity of human alpha-synuclein when expressed in simple organisms can be suppressed by overexpression of endoplasmic reticulum (ER)-to-Golgi transport machinery, suggesting that inhibition of constitutive secretion represents a fundamental cause of the toxicity. Whether similar inhibition in mammals represents a cause of familial Parkinsons disease has not been established. We tested elements of this hypothesis by expressing human alpha-synuclein in mammalian kidney and neuroendocrine cells and assessing ER-to-Golgi transport. Overexpression of wild type or the familial disease-associated A53T mutant alpha-synuclein delayed transport by up to 50%; however, A53T inhibited more potently. The secretory delay occurred at low expression levels and was not accompanied by insoluble alpha-synuclein aggregates or mistargeting of transport machinery, suggesting a direct action of soluble alpha-synuclein on trafficking proteins. Co-overexpression of ER/Golgi arginine soluble N-ethylmaleimide-sensitive factor
TY - JOUR. T1 - Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage. AU - Paiva, Isabel. AU - Pinho, Raquel. AU - Pavlou, Maria Angeliki. AU - Hennion, Magali. AU - Wales, Pauline. AU - Schütz, Anna Lena. AU - Rajput, Ashish. AU - Szego, Éva M.. AU - Kerimoglu, Cemil. AU - Gerhardt, Ellen. AU - Rego, Ana Cristina. AU - Fischer, André. AU - Bonn, Stefan. AU - Outeiro, Tiago F.. PY - 2017/6/15. Y1 - 2017/6/15. N2 - Alpha-synuclein (aSyn) is considered a major culprit in Parkinsons disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional ...
Title:A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies. VOLUME: 19 ISSUE: 6. Author(s):Larisa Ryskalin, Carla L. Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella and Francesco Fornai*. Affiliation:Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126 Pisa, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126 Pisa, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia, I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Isernia. Keywords:Alpha synuclein, synucleinopathies, alpha synuclein aggregates, loss-of-function, co-chaperonine, neurodegeneration, neuroprotection.. Abstract:Alpha synuclein (α-syn) belongs to a class of proteins which ...
Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. Alpha-synuclein is encoded by the SNCA gene in humans and is mainly expressed in the cerebral neocortex, hippocampus, nigra, thalamus, and metencephalon, with the majority of the protein localizing to the presynaptic terminal and nucleus of neuron cells. The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinsons disease, Lewy body dementia (associated with both Alzheimers and Parkinsons disease), and multiple system atrophy. Mutations in the SNCA gene have been associated with the pathogenesis of Parkinson disease.. ...
Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. Alpha-synuclein is encoded by the SNCA gene in humans and is mainly expressed in the cerebral neocortex, hippocampus, nigra, thalamus, and metencephalon, with the majority of the protein localizing to the presynaptic terminal and nucleus of neuron cells. The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinsons disease, Lewy body dementia (associated with both Alzheimers and Parkinsons disease), and multiple system atrophy. Mutations in the SNCA gene have been associated with the pathogenesis of Parkinson disease.. ...
Parkinsons disease (PD) is characterized by a progressive loss of midbrain dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies. Mutations in several genes including alpha-synuclein and parkin have been linked to familial PD. The loss of parkins E3-ligase activity leads to dopaminergic neuronal degeneration in early-onset autosomal recessive juvenile parkinsonism, suggesting a key role of parkin for dopamine neuron survival. To evaluate the potential neuroprotective role of parkin in the pathogenesis of PD, we tested whether overexpression of wild-type rat parkin could protect against the toxicity of mutated human A30P alpha-synuclein in a rat lentiviral model of PD. Animals overexpressing parkin showed significant reductions in alpha-synuclein-induced neuropathology, including preservation of tyrosine hydroxylase-positive cell bodies in the substantia nigra and sparing of tyrosine hydroxylase-positive nerve terminals in the striatum. The parkin-mediated neuroprotection was
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. It is abundant in the brain while smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with phospholipids and proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function ...
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. It is abundant in the brain while smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with phospholipids and proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function ...
We have produced a panel of 32 unique monoclonal antibodies that recognize common structural elements in amyloid aggregates, like the alpha-synuclein aggregates that are believed to play an important role in PD pathogenesis. Although these antibodies were originally produced against Abeta amyloid from Alzheimer s disease, we found that many of them recognize common or generic epitopes (or antibody binding sites) that occur on amyloid aggregates from a number of different amyloids made from different protein sequences. For some of these antibodies, we have already shown that interact with alpha-synuclein aggregates in vitro. In this project, we will test the immunoreactivity of all of the antibodies against alpha-synuclein oligomers and fibrils. We will also test whether any of the antibodies can detect pathological oligomers in human PD brain. Antibodies that react with pathological amyloid aggregates in brain would represent candidates for therapeutic development.. Relevance to ...
Objective/Rationale: Mounting evidence indicates a crucial role of pathological aggregates of the protein alpha-synuclein in Parkinsons disease (PD). Small aggregates termed oligomers seems to be toxic for nerve cells. Moreover, prion-like spread of pathological alpha-synuclein aggregation may cause progressive degeneration of brain areas. We recently developed the novel oligomer modulator anle138b that inhibits the formation of pathological alpha-synuclein oligomers and has shown therapeutic efficacy in several models of PD.Project Description:We will test anle138b in a novel, large PD model. First, we will test which doses are required to obtain relevant levels of anle138b in blood and tissue (
Findings from human patients, yeast and a mouse model imply that defects in polyamine pathway play a role in Parkinsons disease pathogenesis, suggesting that existing drugs may be able to slow progression of the disease, according to a study published Sept. 13 in an early online edition of Proceedings of the National Academy of Sciences.
An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinsons disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We
Accumulating evidence suggests that the lesions of Parkinsons disease (PD) expand due to transneuronal spreading of fibrils composed of misfolded alpha-synuclein (a-syn), over the course of 5-10 years. However, the precise mechanisms and the processes underlying the spread of these fibril seeds have not been clarified in vivo. Here, we investigated the speed of a-syn transmission, which has not been a focus of previous a-syn transmission experiments, and whether a-syn pathologies spread in a neural circuit-dependent manner in the mouse brain. We injected a-syn preformed fibrils (PFFs), which are seeds for the propagation of a-syn deposits, either before or after callosotomy, to disconnect bilateral hemispheric connections. In mice that underwent callosotomy before the injection, the propagation of a-syn pathology to the contralateral hemisphere was clearly reduced. In contrast, mice that underwent callosotomy 24 h after a-syn PFFs injection showed a-syn pathology similar to that seen in mice without
Spark Therapeutics Enters into Definitive Merger Agreement with Roche Spark Therapeutics announced that it has entered into a definitive merger agreement for Roche to fully acquire Spark Therapeutics at a price of $114.50 per share in an all-cash transaction. [Spark Therapeutics, Inc.] Press Release AbbVie and Voyager Therapeutics Announce Collaboration to Develop Vectorized Antibodies to Treat Parkinsons Disease and Other Synucleinopathies AbbVie and Voyager Therapeutics, Inc. announced an exclusive, global strategic collaboration and option agreement to develop and commercialize vectorized antibodies directed at pathological species of alpha-synuclein for the potential treatment of Parkinsons disease and other diseases (synucleinopathies) characterized by the abnormal accumulation of misfolded alpha-synuclein protein. [AbbVie Inc.] Press Release CRISPR Therapeutics and StrideBio Expand Exclusive Development and Option Agreement CRISPR Therapeutics and StrideBio, Inc. announced that a ...
of Lewy Neurites].. I have previously demonstrated to you (with the most excellent Immunostains of Paula at Excalibur Labs) that:. 1. Lewy bodies are marked with Rabbit antibodies to human Alpha Synuclein. 2. Lewy neurites are marked with rabbit antibodies to human Alpha Synuclein. 3. Nematode larval worms contain immunorective proteins to Human Alpha Synuclein. 4. Nematode worms are endowed with their own neurons and their own Glial cells. 5. Synuclein proteins (but not necessarily the toxic variant of Alpha synuclein) are incumbent in Synaptic Structure, and these are located between the Dendritic/Synaptic button apparatus and the Nucleus of the neuron. 6. Borrelia burgdorferi is an EndoSymbiont microbe which dwells inside of the bodies of select nematode worms, larvae, and worm eggs too.. 7. Borrelia burgdorferi might be endowed with a protein which is immune-reactive to the toxic variant of Alpha Synuclein or Borrelia spirochetes may absorb this protein or Borrelia spriochetes may absorb ...
of Lewy Neurites].. I have previously demonstrated to you (with the most excellent Immunostains of Paula at Excalibur Labs) that:. 1. Lewy bodies are marked with Rabbit antibodies to human Alpha Synuclein. 2. Lewy neurites are marked with rabbit antibodies to human Alpha Synuclein. 3. Nematode larval worms contain immunorective proteins to Human Alpha Synuclein. 4. Nematode worms are endowed with their own neurons and their own Glial cells. 5. Synuclein proteins (but not necessarily the toxic variant of Alpha synuclein) are incumbent in Synaptic Structure, and these are located between the Dendritic/Synaptic button apparatus and the Nucleus of the neuron. 6. Borrelia burgdorferi is an EndoSymbiont microbe which dwells inside of the bodies of select nematode worms, larvae, and worm eggs too.. 7. Borrelia burgdorferi might be endowed with a protein which is immune-reactive to the toxic variant of Alpha Synuclein or Borrelia spirochetes may absorb this protein or Borrelia spriochetes may absorb ...
Alpha-Synuclein (aSyn) is a 140 amino acid, intrinsically disordered protein that adopts an extended amphipathic alpha-helical structure upon binding the membrane. aSyn is the major proteinaceous component of insoluble fibrillar Lewy bodies, a hallmark of Parkinsons disease (PD). The precise roles of both native and pathological forms of aSyn remain unclear. However, the interaction of aSyn with cellular membranes is now thought to be critical to its native function, and potentially to its role in PD. In vivo studies with overexpressed aSyn shows a stalling of vesicle fusion at the plasma membrane, whereas in vitro studies of small lipid vesicles and aSyn demonstrate an inhibition of vesicle fusion. In addition, numerous biophysical studies have identified potential curvature sensing and curvature inducing characteristics for aSyn, however the mechanism behind these processes is not well understood. The work in this thesis explores the membrane remodeling capacity of aSyn using a combination of ...
Parkinsons disease - characterized by tremors, rigidity, difficulty walking and other symptoms - is caused by the destruction of brain cells that produce the neurotransmitter dopamine. In recent years researchers at several centers have been studying the role of alpha-synuclein accumulations in dopamine-producing neurons, observed in patients with both inherited and sporadic Parkinsons disease. MGH-MIND investigators have discovered that, in Parkinsons, the alpha-synuclein molecule folds abnormally and form aggregates called inclusion bodies. Such inclusions of other abnormal proteins are seen in several disorders, but whether inclusions are toxic or protective to neurons has been controversial.. In a paper published last year in the Proceedings of the National Academy of Sciences, a research team led by Kazantsev analyzed ways to reduce the size of inclusions containing misfolded versions of alpha-synuclein or of the Huntingtons disease-associated protein huntingtin. They found that a ...
Alpha synuclein is normally found in neurons, particularly at synapses. When it misfolds, it begins to cause damage. To directly test the gut to brain hypothesis, the researchers injected misfolded alpha synuclein fibrils directly into the muscular wall of the gut in mice, at the point where the stomach empties into the first part of the small intestine, called the duodenum. These fibrils began interacting with the alpha synuclein found in local nerves in the gut, triggering a further misfolding process.. One month later, the researchers found misfolded alpha synuclein in the brain, specifically at the point at which the vagus nerve originates. Within 3 months, misfolded alpha synuclein could be found in other parts of the brain, including the substantia nigra, the main dopamine centre which is involved in movement, and by 7 months, alpha synuclein could clearly be seen in this region.. The team then addressed the effects of cutting the vagus nerve in mice that had been injected with preformed ...
The role of phosphorylation at Y125 in regulating the structure, aggregation, and membrane binding of alpha-synuclein: Implications for the pathogenesis of Parkinsons disease : The role of phosphorylation at Y125 in regulating the structure, aggregation, and membrane binding of alpha-synuclein: Implications for the pathogenesis of Parkinsons disease
Marxreiter, Franz; Ettle, Benjamin; May, Verena E. L.; Esmer, Hakan; Patrick, Christina; Kragh, Christine Lund; Klucken, Jochen; Winner, Beate; Riess, Olaf; Winkler, Juergen; Masliah, Eliezer; Nuber, Silke ...
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 (aSyn) is a central player in Parkinsons disease (PD) but the precise molecular mechanisms underlying its pathogenicity remain unclear. It has recently been suggested that nuclear aSyn may modulate gene expression, possibly via interactions with DNA. However, the biological behavior of aSyn in the nucleus and the factors affecting its transcriptional role are not known. Here, we investigated the mechanisms underlying aSyn-mediated transcription deregulation by assessing its effects in the nucleus and the impact of phosphorylation in these dynamics. We found that aSyn induced severe transcriptional deregulation, including the downregulation of important cell cycle-related genes. Importantly, transcriptional deregulation was concomitant with reduced binding of aSyn to DNA. By forcing the nuclear presence of aSyn in the nucleus (aSyn-NLS), we found the accumulation of high molecular weight aSyn species altered gene expression and reduced toxicity when compared with the wild-type or ...
Our findings further support the causative role of soluble amyloid oligomers in triggering neurodegeneration and shed light into the mechanisms by which these species cause neuronal damage, which, we show here, can be amenable to modulation through the use of metal chelation.
AURORA, Colo. (Dec. 22, 2017) - While vigorous exercise on a treadmill has been shown to slow the progression of Parkinsons disease in patients, the molecular reasons behind it have remained a mystery.. But now scientists at the University of Colorado Anschutz Medical Campus may have an answer.. For the first time in a progressive, age-related mouse model of Parkinsons, researchers have shown that exercise on a running wheel can stop the accumulation of the neuronal protein alpha-synuclein in brain cells.. The work, published Friday in the journal PLOS ONE, was done by Wenbo Zhou, PhD, research associate professor of medicine and Curt Freed, MD, professor of medicine and division head of the Division of Clinical Pharmacology and Toxicology at the CU School of Medicine.. The researchers said clumps of alpha-synuclein are believed to play a central role in the brain cell death associated with Parkinsons disease. The mice in the study, like humans, started to get Parkinsons symptoms in ...
In this special issue of Neuropathology and Applied Neurobiology on synucleinopathies, leading investigators provide an overview of this vibrating field. A basic understanding is at hand and it appears increasingly likely that safe and effective mechanism-based therapies for synucleinopathies will be developed. They will probably be aimed at prevention rather than at treating already existing disease. PD stands out among neurodegenerative diseases, in that an effective symptomatic therapy in the form of dopamine replacement already exists. In the first contribution, Roger Barker and Caroline Williams-Gray provide a comprehensive overview of the clinical features of PD and compare them with those of other synucleinopathies (1). In the second article, Nadia Stefanova and Gregor Wenning focus on the rarer, but more aggressive, MSA, which is divided into parkinsonian (MSA-P) and cerebellar (MSA-C) forms, with many cases having features of both (mixed-type MSA) (2). Autonomic dysfunction is a major ...
When misfolded, the protein alpha-synuclein becomes toxic to neurons and is a key pathological culprit in Parkinsons. It is therefore an important target for disease-modification. Immunotherapy in Parkinsons attempts to use immune cells, and specifically the antibodies they generate, to target misfolded alpha-synuclein to inactivate it.
Lewy bodies of a-synuclein protein are prominent characteristics in the Parkinsons disease (PD) pathology. The mechanism of Lewy body formation and consequent cytotoxicity was studied by Brandis et al. (2006) in a newly developed model organism of fission yeast. Though, the level of a-synuclein expression studied was either high or low, the wild-type and A53T familial mutant of a-synuclein followed the nucleation polymerization theory in the process of misfolding and aggregating. At high concentration, a-synuclein formed cytoplasmic aggregates in a concentration and time-dependent manner. However, these aggregates appeared to be independent of cytotoxicity. In this current study, the fission yeast model is used again but to evaluate a-synuclein misfolding, aggregation, and non-toxic properties when expression is moderate. The results indicate moderate a-synuclein expression to obey the nucleation polymerization model. In light of this study, a-synuclein aggregation requires a necessary threshold
Parkinsons disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)-containing intraneuronal inclusions-Lewy bodies (LBs) and Lewy neurites (LNs)-in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other brain regions. However, a cause-and-effect relationship between LB/LN formation and neurodegeneration remains unclear. Indeed, whether LB/LNs are toxic or represent a neuroprotective response has been contentious. Luk et al. (p. 949) injected α-Syn fibrils generated from recombinant mouse α-Syn protein into the dorsal striatum of wild-type mice and found that misfolded α-Syn caused the formation of PD-like LB/LNs and subsequent cell-to-cell transmission of pathologic α-Syn to anatomically interconnected regions, including the SNpc. Furthermore, the formation of LB/LNs and their accumulation in SNpc resulted in the progressive loss of these dopaminergic neurons, reduced dopamine innervations to ...
Insoluble and fibrillar forms of α-synuclein are the major components of Lewy bodies, a hallmark of several sporadic and inherited neurodegenerative diseases known as synucleinopathies. α-Synuclein is a natural unfolded and aggregation-prone protein that can be degraded by the ubiquitin-proteasomal system and the lysosomal degradation pathways. α-Synuclein is a target of the main cellular proteolytic systems, but it is also able to alter their function further, contributing to the progression of neurodegeneration. Aging, a major risk for synucleinopathies, is associated with a decrease activity of the proteolytic systems, further aggravating this toxic looping cycle. Here, the current literature on the basic aspects of the routes for α-synuclein clearance, as well as the consequences of the proteolytic systems collapse, will be discussed. Finally, particular focus will be given to the sirtuinss role on proteostasis regulation, since their modulation emerged as a promising therapeutic strategy to
Detect and quantitate human Alpha-synuclein in biological fluids such as serum, plasma, cerebrospinal fluid and cell culture supernatants using a homogeneous AlphaLISA no-wash assay.
The alpha-synuclein (alpha-syn) protein is clearly implicated in Parkinsons disease (PD). Mutations or triplication of the alpha-syn gene leads to early onset PD, possibly by accelerating alpha-syn oligomerization. alpha-syn interacts with lipids, and this membrane binding activity may relate to it …
Understanding the molecular pathogenesis of Parkinsons disease (PD) is a priority in biomedical research and a pre-requisite to improve early disease diagnosis and ultimately to developing disease-modifying strategies. In the past decade and a half, geneticists have identified several genes that are involved in the molecular pathogenesis of PD. They not only identified gene variants segregating with familial forms of PD but also genetic risk factors of sporadic PD via genome-wide association studies (GWAS). Understanding how PD genes and their gene products function holds the promise of unraveling key PD pathogenic processes. Therefore the precise cellular role of PD proteins is currently the subject of intense investigation. Interestingly, a number of PD proteins have enzymatic functions, including kinase, GTPase or ATPase functions. In the context of understanding disease pathogenesis or developing disease-modifying therapies, enzymes possess several useful features. Firstly, enzymes are
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Parkinsons disease is the second most common neurodegenerative disorder[31] and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinsons disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinsons disease. The mechanism by which the brain cells in Parkinsons are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteasome. This protein accumulation forms proteinaceous ...
Parkinsons disease is the second most common neurodegenerative disorder[31] and manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Parkinsons disease is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. The following paragraph is an excerpt from the Pathophysiology section of the article Parkinsons disease. The mechanism by which the brain cells in Parkinsons are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteasome. This protein accumulation forms proteinaceous ...
Health,... This news release is available in a onClick NewPopupWindow(t...In Parkinsons disease the protein alpha-synuclein aggregates and a...Parkinsons disease is a disorder of the nervous system. It typically ...At the present no cure exists for Parkinsons disease although sympt...,Proteins,in,migration,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
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 ...
TY - JOUR. T1 - Low alpha-synuclein 126 mRNA levels in dementia with Lewy bodies and Alzheimer disease. AU - Beyer, Katrin. AU - Humbert, Jordi. AU - Ferrer, Anna. AU - Lao, José I.. AU - Carrato, Cristina. AU - López, Dolores. AU - Ferrer, Isidro. AU - Ariza, Aurelio. PY - 2006/8/1. Y1 - 2006/8/1. N2 - Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration. Three different isoforms (α-synuclein 112, 126, and 140) resulting from alternative splicing have been described so far. The present study explores α-synuclein 126 mRNA expression levels in the prefrontal cortex of six patients with dementia with Lewy bodies, eight patients with Lewy body variant of Alzheimer disease, eight patients with Alzheimer disease, and 10 controls. Relative α-synuclein 126 expression levels were determined by real-time polymerase chain reaction with competimer technology. Alpha-synuclein 126 mRNA expression was ...
TY - JOUR. T1 - Translation initiator EIF4G1 mutations in familial parkinson disease. AU - Chartier-Harlin, Marie Christine. AU - Dachsel, Justus C.. AU - Vilariño-Güell, Carles. AU - Lincoln, Sarah J.. AU - Leprêtre, Frédéric. AU - Hulihan, Mary M.. AU - Kachergus, Jennifer. AU - Milnerwood, Austen J.. AU - Tapia, Lucia. AU - Song, Mee Sook. AU - Le Rhun, Emilie. AU - Mutez, Eugénie. AU - Larvor, Lydie. AU - Duflot, Aurélie. AU - Vanbesien-Mailliot, Christel. AU - Kreisler, Alexandre. AU - Ross, Owen A.. AU - Nishioka, Kenya. AU - Soto-Ortolaza, Alexandra I.. AU - Cobb, Stephanie A.. AU - Melrose, Heather L.. AU - Behrouz, Bahareh. AU - Keeling, Brett H.. AU - Bacon, Justin A.. AU - Hentati, Emna. AU - Williams, Lindsey. AU - Yanagiya, Akiko. AU - Sonenberg, Nahum. AU - Lockhart, Paul J.. AU - Zubair, Abba C.. AU - Uitti, Ryan J.. AU - Aasly, Jan O.. AU - Krygowska-Wajs, Anna. AU - Opala, Grzegorz. AU - Wszolek, Zbigniew K.. AU - Frigerio, Roberta. AU - Maraganore, Demetrius M.. AU - ...
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 ...
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 ...
Parkinson s disease (PD) is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer s disease. The neuropathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra of the midbrain and protein aggregation, called Lewy bodies and Lewy neurites, which are primarily contributed by misfolded a-synuclein. Increasing evidence shows that exogenous human a-synuclein fibrils originating from the PD patient brain, trans- genic mouse brain or recombinantly synthesized from bacteria, can be taken up into neurons and stimulate the aggregation of endogenous a-synuclein in cell models or in laboratory animal models after injection into the central and peripheral nervous systems.This consortium aims to address fundamental questions on the origin and the molecular mechanisms causing the development of synucleinopathies and to design innovative protective strategies, with combined cutting-edge technologies and complementary and ...
Multiple system atrophy (MSA) is a horrible and unrelenting neurodegenerative disorder with an uncertain etiology and pathophysiology. MSA is a unique proteinopathy in which alpha-synuclein (α-syn) accumulates preferentially in oligodendroglia rather than neurons. Glial cytoplasmic inclusions (GCIs) of α-syn are thought to elicit changes in oligodendrocyte function, such as reduced neurotrophic support and demyelination, leading to neurodegeneration. To date, only a murine model using one of three promoters exist to study this disease. We sought to develop novel rat and nonhuman primate (NHP) models of MSA by overexpressing α-syn in oligodendroglia using a novel oligotrophic adeno-associated virus (AAV) vector, Olig001. To establish tropism, rats received intrastriatal injections of Olig001 expressing GFP. Histological analysis showed widespread expression of GFP throughout the striatum and corpus callosum with ,95% of GFP+ cells co-localizing with oligodendroglia and little to no expression ...
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
Parkinsons disease is a movement disorder characterized by nigrostriatal dopamine pathway degeneration and neuronal α-synuclein accumulation. Pathogenesis is associated with mutations in α-synuclein and Gba1 encoding alleles. Animal models created to date do not recapitulate the spectrum of clinical disease features. This thesis characterizes the bi-genic Synergy mouse, hypothesized to demonstrate motor behavioural and histological abnormalities downstream of α-synuclein overexpression and mutated Gba1. Synergy and SNCA mice (overexpressed α-synuclein with wild-type Gba1) have early onset deficits in motor coordination, muscle strength and nest building. Both exhibit increased α-synuclein concentration in the brain and cerebellar inclusions positive for two markers of pathological α-synuclein processing. Overall mutant Gba1 expression within Synergy mice does not worsen the behaviour or the histopathological findings associated with overexpression of human α-synuclein in SNCA mice. ...
Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed to test for association under additive and recessive modes of inheritance after adjusting for gender and age. No result met genomewide significance based on a conservative Bonferroni correction. The strongest association result was with SNPs in the GAK/DGKQ region on chromosome 4 (additive model: p = 3.4 × 10-6; OR = 1.69). Consistent evidence of association was also observed to the chromosomal regions containing SNCA (additive model: p = 5.5 × 10-5; OR = 1.35) and MAPT (recessive model: p = 2.0 × ...
Accumulation of the α-synuclein (α-syn) protein is a hallmark of a group of brain disorders collectively known as synucleinopathies. The mechanisms responsible for α-syn accumulation are not well understood. Several studies suggest a link between synucleinopathies and the cholesterol metabolite 27-hydroxycholesterol (27-OHC). 27-OHC is the major cholesterol metabolite in the blood that crosses the blood brain barrier, and its levels can increase following hypercholesterolemia, aging, and oxidative stress, which are all factors for increased synucleinopathy risk. In this study, we determined the extent to which 27-OHC regulates α-syn levels in human dopaminergic neurons, the cell type in which α-syn accumulates in PD, a major synucleinopathy disorder. Our results show that 27-OHC significantly increases the protein levels, not the mRNA expression of α-syn. The effects of 27-OHC appear to be independent of an action through liver X receptors (LXR), its cognate receptors, as the LXR agonist, GW3965,
en] Dermal fibroblasts from a patient carrying a heterozygous c.88G , C mutation in the SNCA gene that encodes alpha-synuclein were reprogrammed to pluripotency by retroviruses. This pathogenic mutation generates the p.A30P form of the alpha-synuclein protein leading to autosomal dominantly inherited Parkinsons disease (PD). Two clonal iPS cell lines were generated (A30P-3 and A30P-4) and characterised by validating the silencing of viral transgenes, the expression of endogenous pluripotency genes, directed differentiation into three germ layers in-vitro and a stable molecular genotype. These iPSC lines will serve as a valuable resource in determining the role of the p.A30P SNCA mutation in PD pathogenesis ...
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Currently, there are no treatments that can slow or stop the progression of neuron death in multiple system atrophy (MSA). Survival for patients is usually around 8-10 years from symptom onset. In patients with MSA, neurodegeneration is caused by the abnormal and progressive accumulation of the protein alpha-synuclein in neurons and glia. Alpha-synuclein, and other…
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
Background: The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD). Objective: To evaluate the influence of heterozygosity for parkin mutation on onset age in a sample of families with at least 2 PD-affected members. Design: Clinical and genetic study. Setting: Twenty collaborative clinical sites. Patients: Patients with familial PD collected in the GenePD study. Studied families were selected for (1) affected sibling pairs sharing 2 alleles identical by state at PARK2 (D6S305) or (2) 1 or more family members with onset age younger than 54 years, regardless of D6S305 status. At least 1 member from each of 183 families underwent comprehensive screening for deletion/insertion variants and point mutations in PARK2. Main Outcome Measures: Mutations in the parkin gene were screened by means of single-stranded conformation polymorphism and sequencing in all 12 coding exons and flanking intronic sequences for point ...
Author: Koch, J. C. et al.; Genre: Journal Article; Published online: 2015-07-09; Open Access; Title: Alpha-synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons.
TY - JOUR. T1 - Correction. T2 - Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport (Scientific Reports DOI: 10.1038/s41598-017-15575-3). AU - Toba, Shiori. AU - Jin, Mingyue. AU - Yamada, Masami. AU - Kumamoto, Kanako. AU - Matsumoto, Sakiko. AU - Yasunaga, Takuo. AU - Fukunaga, Yuko. AU - Miyazawa, Atsuo. AU - Fujita, Sakiko. AU - Itoh, Kyoko. AU - Fushiki, Shinji. AU - Kojima, Hiroaki. AU - Wanibuchi, Hideki. AU - Arai, Yoshiyuki. AU - Nagai, Takeharu. AU - Hirotsune, Shinji. N1 - Publisher Copyright: © 2018 The Author(s).. PY - 2018/12/1. Y1 - 2018/12/1. N2 - In this Article, Figure 5 was inadvertently published as Figures 5 and 6, leading to the incorrect publication of Figure 6 as Figure 7 and the omission of the correct Figure 7. The correct Figures 5, 6, and 7 appear below as Figures 1, 2, and 3 respectively. The Figure legends are correct. (Figure Presented).. AB - In this Article, Figure 5 was inadvertently ...
Parkinsons disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates (Lewy neurites) in processes of gut enteric and vagal motor neurons. Rost
Multiple missense mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with familial forms of late onset Parkinsons disease (PD), the most common age-related movement disorder. The dysfunction of dopamine transmission contributes to PD-related motor symptoms. Interestingly, LRRK2 is more abundant in the dopaminoceptive striatal spiny projection neurons (SPNs) compared to the dopamine-producing nigrostriatal dopaminergic neurons. Aging is the most important risk factor for PD and other neurodegenerative diseases. However, whether LRRK2 modulates the aging of SPNs remains to be determined. We conducted RNA-sequencing (RNA-seq) analyses of striatal tissues isolated from Lrrk2 knockout (Lrrk2−/−) and control (Lrrk2+/+) mice at 2 and 12 months of age. We examined SPN nuclear DNA damage and epigenetic modifications; SPN nuclear, cell body and dendritic morphology; and the locomotion and motor skill learning of Lrrk2+/+ and Lrrk2−/− mice from 2 to 24 months of age. Considering the strength
Mavroeidi, P.; Arvanitaki, F.; Karakitsou, A. K.; Vetsi, M.; Kloukina, I.; Zweckstetter, M.; Giller, K.; Becker, S.; Sorrentino, Z. A.; Giasson, B. I. et al.; Jensen, P. H.; Stefanis, L.; Xilouri, M.: Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models. Acta Neuropathologica 138 (3), pp. 415 - 441 (2019 ...
Mavroeidi, P.; Arvanitaki, F.; Karakitsou, A. K.; Vetsi, M.; Kloukina, I.; Zweckstetter, M.; Giller, K.; Becker, S.; Sorrentino, Z. A.; Giasson, B. I. et al.; Jensen, P. H.; Stefanis, L.; Xilouri, M.: Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models. Acta Neuropathologica 138 (3), pp. 415 - 441 (2019 ...
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…
Global Markets Directs, Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) - Pipeline
Patients suffer from a broad spectrum of gastrointestinal symptoms, says Scheperjans. That is, he and other physicians have documented that PD and gastrointestinal problems go hand in hand-with constipation, for example, often appearing years before the onset of motor symptoms.. Not only that, says Scheperjans-In the gastrointestinal tract of PD patients, similar neuropathological changes have been described as in the brain. The mis-folded protein (alpha-synuclein) that is found in the brains of those with PD has also been identified in patients intestines (more specifically: in the enteric nervous system of the gut) even before the neurodegeneration is advanced enough to affect movement. This leads researchers to think the protein could somehow be involved in causing the disease.. Research from Scheperjans team found gut microbiota changes in those with PD, which correlated with their motor symptoms: as a group of bacteria called Enterobacteriaceae increased, so did the severity of ...
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 ...
These ROSA26-LRRK2 (R1441C) mice allow |i|cre|/i|-inducible expression of the familial Parkinsons disease-associated R1441C missense mutant form of |i|LRRK2|/i|, and may be useful for studying Parkinsons disease pathogenesis and neurodegeneration.
mail03.med.uni-muenchen.de. Before joining our group in May 2017, Karsten studied Molecular Biology and Biomedicine at the Johannes Gutenberg-University Mainz. He joined the group of Christian Behl (Johannes Gutenberg-University Mainz) to obtain his masters degree, where he worked on the effects of altered autophagy on the oligomerization and aggregation behavior of alpha-synuclein species as well as their release via exosomes. In his PhD he is trying to elucidate the crosstalk between early secretory processes and autophagy. Both processes are initiated at specific sites of the endoplasmic reticulum and are crucial to maintain cell homeostasis. His project focusses on the identification of unknown interaction partners and shared regulators of both pathways, e.g. by using high-throughput microscopy. ...
CliniCrowd is driven by pre-clinical studies conducted by Professor Daniel Segal and Professor Ehud Gazit at Tel Aviv University in Israel and by Professor Eliezer Masliah at University of California, San Diego. See publication. Alpha synuclein is an abundant protein in the brain especially in the presynaptic terminal of neurons. It plays a role in maintaining vesicles for the neurotransmitters in the nerve endings. Parkinsons disease (PD) is characterized by degeneration and loss of neurons particularly those crucial for coordination of movements. According to the Michael J. Fox Foundation it is the pathological hallmark of Parkinsons. There has been significant research in the areas of preventing excess alpha synuclein formation or clumping and disruption of the already existing clumps.. Mannitol, a common low calorie sweetener, found by the FDA to be generally recognized as safe (GRAS) food additive, see link to FDA site and link to EFSA site, has shown the ability to diminish alpha ...
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…
The small SynuClean-D molecule interrupts the formation of the alpha-synuclein amyloid fibres responsible for the onset of Parkinsons disease, ...
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... ...
Renowned researcher Alice Lazzarini, PhD chronicles the connection between pα-syn, tau, and mitochondrial degradation, and how it may lead to new treatments.
The demonstration of proteinaceous inclusions in the brain is the key step in the pathological diagnosis of degenerative dementias. The diversity of these diseases has necessitated the use of a panel of (immuno)stains to visualize all suspect pathologies, elevating diagnostic costs. Immunodetection of p62 (sequestosome 1), an abundant constituent in diverse pathological inclusions, holds the potential for a broad-specificity, high-contrast inclusion label. In the brain, pathological p62-positive aggregates comprise both cytoplasmic and nuclear types in neurones and glia, with abnormal tau, alpha-synuclein, TAR DNA-binding protein 43 or polyglutamine proteins as primary components. We therefore set out to evaluate the performance of p62 antibodies for diagnostic immunohistochemistry. We optimized the application conditions and compared the staining profiles of eight commercial p62 antibodies with each other and with reference immunostains, using 2-mm tissue multiarrays representing the major ...
Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of ... alpha-synuclein: can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as ... Alpha-synuclein can damage membranes by inducing membrane curvature,[12] and cause extensive tubulation and vesiculation when ...
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature ... alpha-synuclein was discovered to be the major component of Lewy bodies within brain cells of PD patients; according to the ... alpha-synuclein. Lazzarini worked with the Italian Instituto de Scienze Neurologiche to get blood samples from the family ... that fragments of alpha-synuclein bind to other proteins to form the Lewy body, an insoluble proteinaceous material ...
The NIH team and a team led by Maria Grazia Spillantini reported on alpha-synuclein deposits in Lewy bodies as well as alpha- ... Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997). "Alpha-synuclein in Lewy bodies". Nature. 388 ( ... Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998). "Alpha synuclein in neurodegenerative disorders ... 1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045-7. doi ...
... alpha-synuclein. Within days of the publication of the PARK1 findings, alpha-synuclein was discovered to be the major component ... Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature ... Schulz-Schaeffer WJ (August 2010). "The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, ... "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045-7. doi:10.1126 ...
A modified form of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with ... Arima K, Uéda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (November 1998). "NACP/alpha-synuclein ... A post-translationally modified form of the protein called alpha-synuclein may be a causal agent for the disease. probably ... The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. Mutations ...
Preclinical research also targets alpha-synuclein. Selegiline is in a group of medications called monoamine oxidase type B (MAO ...
Moussaud S, Jones DR, Moussaud-Lamodière EL, Delenclos M, Ross OA, McLean PJ (October 2014). "Alpha-synuclein and tau: ... Tauopathies are often overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins. ...
Alpha-synuclein modulates DNA repair processes, including the repair of DNA double-strand breaks by the non-homologous end ... Alpha-synuclein deposits can affect the cardiac muscle and blood vessels. Almost all people with synucleinopathies have ... The DNA repair function of alpha-synuclein appears to be compromised in Lewy body inclusion bearing neurons, and this may ... October 2014). "Alpha-synuclein and tau: teammates in neurodegeneration?". Mol Neurodegener. 9: 43. doi:10.1186/1750-1326-9-43 ...
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 ...
Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as ... it is alpha-synuclein. In Huntington's disease, it is huntingtin. Transglutaminase substrates: Amyloid-beta, tau, alpha- ... Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. The main known risk factor is age. Mutations ... Notably, alpha-synuclein-ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. ...
... 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 ...
Lee FJ, Liu F, Pristupa ZB, Niznik HB (April 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 (April 2003). "Attenuation of dopamine transporter activity by alpha-synuclein". Neuroscience Letters. 340 ...
"Glycosylation as an Inhibitor of Alpha-synuclein Aggregation". The Michael J. Fox Foundation for Parkinson's Research , ... As O-GlcNAc modification of α-synuclein has been found to inhibit its aggregation, elevating α-synuclein O-GlcNAc is being ... Solid-phase peptide synthesis was used to prepare full-length α-synuclein with an O-GlcNAc modification at T72. Thioflavin T ... For example, a nanobody recognizing a C-terminal EPEA sequence can direct OGT enzymatic activity to α-synuclein. Apoptosis, a ...
Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC (November 2005). "Alpha-synuclein cooperates with CSPalpha in ... 2005). "Characterization of the G alpha(s) regulator cysteine string protein". J. Biol. Chem. 280 (34): 30236-41. doi:10.1074/ ... "The synaptic vesicle protein CSP alpha prevents presynaptic degeneration". Neuron. 42 (2): 237-51. doi:10.1016/S0896-6273(04) ... encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis". American Journal ...
"Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein". The Journal of Biological Chemistry. 275 ( ... Pronin AN, Morris AJ, Surguchov A, Benovic JL (Aug 2000). "Synucleins are a novel class of substrates for G protein-coupled ... Zhou H, Yan F, Tai HH (Sep 2001). "Phosphorylation and desensitization of the human thromboxane receptor-alpha by G protein- ...
December 2017). "Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes". The Journal of Neuroscience. 37 ...
... the primary structural component of which is alpha-synuclein. Cortical Lewy bodies are also composed of alpha-synuclein fibrils ... "Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders". Sci Rep. 2019 ... Alpha-synuclein modulates DNA repair processes, including repair of DNA double-strand breaks (DSBs) by the process of non- ... Ishizawa T, Mattila P, Davies P, Wang D, Dickson DW (April 2003). "Colocalization of tau and alpha-synuclein epitopes in Lewy ...
... and Lewy bodies and neurites were found to be immunoreactive for alpha-synuclein. Thus, alpha-synuclein aggregation as the ... and reducing amyloid beta or alpha-synuclein accumulation. Therapies under study as of 2019 aim to reduce brain levels of alpha ... The role of alpha-synuclein deposits is unclear, because individuals with no signs of DLB have been found on autopsy to have ... Rarely, mutations in SNCA, the gene for alpha-synuclein, or LRRK2, a gene for a kinase enzyme, can cause any of DLB, ...
The Road to Alpha-Synuclein Oligomerization in PD". Parkinson's Disease. 2011: 693761. doi:10.4061/2011/693761. PMC 3026982. ... Mutations of synuclein alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... Parkinson's disease is characterized by inclusions of a protein called alpha-synuclien (Lewy bodies) in affected neurons that ...
... overexpression in human neuroglioma cells transfected with mutant alpha-synuclein led to 50% less oligomeric alpha- ... April 2008). "Formation of toxic oligomeric alpha-synuclein species in living cells". PLOS ONE. 3 (4): e1867. Bibcode:2008PLoSO ... In breast cancer cell line (MCF7) has been found that not only Hsp90 interacted with estrogen receptor alpha (ERα) but also ... C-terminal domain - rich in alpha helical structure acts as a 'lid' for the substrate binding domain. The helical subdomain ...
"Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications". Ann Neurol. 55 (2): 174-9. doi:10.1002/ ...
It inhibits PTK2B/RAFTK activity and regulates alpha-synuclein phosphorylation. It interacts with Signal-regulatory protein ... and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein ... RA receptor alpha in acute promyelocytic leukemia cells". The Journal of Biological Chemistry. 276 (25): 22375-81. doi:10.1074/ ... alpha and directs integrin-activated cytoskeletal reorganization in macrophages. GRCh38: Ensembl release 89: ENSG00000005020 - ...
Junn E, Lee KW, Jeong BS, Chan TW, Im JY, Mouradian MM (August 2009). "Repression of alpha-synuclein expression and toxicity by ... Doxakis E (April 2010). "Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153". The Journal of ...
Esteves, AR; Arduíno, DM; Silva, DF; Oliveira, CR; Cardoso, SM (2011). "Mitochondrial Dysfunction: The Road to Alpha-Synuclein ... Additionally, in the microenvironment of cancer cells, there is an increase in hypoxia-inducible transcription factor 1-alpha ( ...
Chen, M.; Margittai, M.; Chen, J.; Langen, R. (2007). "Investigation of alpha-Synuclein Fibril Structure by Site-directed Spin ... to understand the structure of amyloid fibrils and the structure of membrane bound Parkinson's disease protein alpha-synuclein ...
DNA damages caused by oxidative stress can be repaired by processes modulated by alpha-synuclein. Alpha synuclein is expressed ... Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders. Sci Rep. 2019 Jul ... For one, dopaminergic neurons show abnormalities in mitochondrial complex 1, causing aggregation of alpha-synuclein; this can ... "Parkin cleaves intracellular alpha-synuclein inclusions via the activation of calpain". The Journal of Biological Chemistry. ...
In addition, alpha-synuclein activates the non-homologous end joining DNA repair pathway. The aggregation of alpha-synuclein in ... alpha-synuclein, is the main component of the Lewy bodies that accumulate in the brains of people with PD. Alpha-synuclein ... alpha-synuclein becomes misfolded and clump together with other alpha-synuclein. Cells are unable to remove these clumps and ... In 1997, alpha-synuclein was found to be the main component of Lewy bodies by Spillantini, Trojanowski, Goedert and others. ...
Olanow CW, Brundin P (January 2013). "Parkinson's disease and alpha synuclein: is Parkinson's disease a prion-like disorder?". ... was hypothesized to be caused by a prion form of alpha-synuclein. Prions form abnormal aggregates of proteins called amyloids, ... the misfolded form of a protein called alpha-synuclein. The endogenous, properly folded form of the prion protein is denoted ... Alzheimer's and Parkinson's diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein". Science. 349 (6248 ...
Singleton AB (August 2005). "Altered alpha-synuclein homeostasis causing Parkinson's disease: the potential roles of dardarin ... "Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein ...
Vallenius T، Luukko K، Mäkelä TP (2000). "CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4 ... binds to alpha-actinin-1 and associates with actin filaments and stress fibers in activated platelets and endothelial cells.". ...
Sharma N, Brandis KA, Herrera SK, Johnson BE, Vaidya T, Shrestha R, Debburman SK (2006). "alpha-Synuclein budding yeast model: ... These β interactions are mediated mainly by salt bridges and hydrophobic interactions between conserved alpha helices whose ... α-synuclein, the major protein component of Lewy bodies, under conditions of low proteasome activity.[97] Impaired proteasomal ... which serve as docking domains for the regulatory particles and the alpha subunits N-termini (Pfam PF10584) form a gate that ...
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 ...
... the primary structural component of which is alpha-synuclein. Cortical Lewy bodies are also composed of alpha-synuclein fibrils ... A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin,[10] neurofilament ... Top panels show a 60-times magnification of the alpha-synuclein intraneuronal inclusions aggregated to form Lewy bodies. The ... Popescu A, Lippa CF, Lee VM, Trojanowski JQ (December 2004). "Lewy bodies in the amygdala: increase of alpha-synuclein ...
In an alpha-synuclein overexpressing Drosophila model of PD, vorinostat (as well as sodium butyrate) reduced alpha-synuclein- ... Hallmarks include mutations to the alpha-synuclein gene, SNCA, as well as PARK2, PINK1, UCHL1, DJ1, and LRRK2 genes, and ... alpha-synuclein, the protein encoded by SNCA, can associate with histones and prevent their acetylation in concert with the ... In an inducible rat model of PD, valproic acid had a neuroprotective effect by preventing translocation of alpha-synuclein into ...
2002). "alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling ...
Preclinical research also targets alpha-synuclein.[129] A vaccine that primes the human immune system to destroy alpha- ... SNCA gene mutations are important in PD because the protein which this gene encodes, alpha-synuclein, is the main component of ... Scientists sometimes refer to Parkinson's disease as a synucleinopathy (due to an abnormal accumulation of alpha-synuclein ... alpha-synuclein was found to be the main component of Lewy bodies by Spillantini, Trojanowski, Goedert and others.[57] ...
... "alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356" ...
Dubois T، Zemlickova E، Howell S، Aitken A (February 2003). "Centaurin-alpha 1 associates in vitro and in vivo with nucleolin ...
Ciosk R، Shirayama M، Shevchenko A، Tanaka T، Toth A، Shevchenko A، Nasmyth K (2000). "Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins". Molecular Cell. 5 (2): 243-54. PMID 10882066. doi:10.1016/S1097-2765(00)80420-7. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription ...
... is activated by PGC1-alpha and promotes reduction of htt aggregation and neurotoxicity in a mouse model of Huntington ... "TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity". Proc Natl Acad Sci USA. 110 (19): 1817- ... clinicopathologic features and demonstration of the specific alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA ... "Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation". Proceedings of the ...
Suh YH; Checler F (September 2002). "Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and ...
Alpha-2-Macroglobulin. *Alpha-synuclein. *Amylin. *Aquaporin 1. *Arachidonate 5-lipoxygenase. *Atrophin 1 ...
Synuclein. *Alpha-synuclein. *Beta-synuclein. *Gamma-synuclein. Other. *Agrin. *Chimerin. *Granin *Chromogranin A ...
"Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments". J. Biol. Chem. ...
The Epstein-Barr virus has been implicated in disorders related to alpha-synuclein aggregation (e.g. Parkinson's disease, ... "Monoclonal antibodies against Epstein-Barr virus cross-react with alpha-synuclein in human brain". Neurology. 55 (9): 1398-401 ...
alpha-actinin binding. • cation channel activity. • identical protein binding. • sour taste receptor activity. ... muscle alpha-actinin binding. • calcium channel activity. • cation transmembrane transporter activity. • calcium-activated ...
... mainly when they are characterized by abnormal accumulation of alpha-synuclein, such as multiple system atrophy (MSA), ... The brain transitions from alpha waves having a frequency of 8-13 Hz (common in the awake state) to theta waves having a ... The onset of sleep involves slowing down of this frequency to the drowsiness of alpha (8-12 Hz) and finally to theta (4-10 Hz) ... the alpha waves of the previous stage are interrupted by abrupt activity called sleep spindles (or thalamocortical spindles) ...
NGF is initially in a 7S, 130-kDa complex of 3 proteins - Alpha-NGF, Beta-NGF, and Gamma-NGF (2:1:2 ratio) when expressed. This ...
... two dementias characterized by abnormal deposits of the protein alpha-synuclein in the brain.[2][3][4] ...
Nagase T، Seki N، Ishikawa K، وآخرون. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321-9, 341-54. PMID 9039502. doi:10.1093/dnares/3.5.321. ...
目前還無法確定路易氏體失智症的確切原因[7],不過和神經中α-突觸核蛋白(英语:Alpha-synuclein)異常團塊的
Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B (1999). "alpha-Synuclein shares physical and ...
... alpha-synuclein in Parkinson's disease, and TDP-43 in Amyotrophic Lateral Sclerosis (ALS) and frontotemporal degeneration. He ... "Biology of Synuclein and Cortical Lewy Bodies Associated with Dementia in AD, LBD, and PD" (July, 2001) and "Genetics of ...
"Endonuclease G interacts with histone H2B and DNA topoisomerase II alpha during apoptosis". Molecular and Cellular Biochemistry ... "Endonuclease G mediates α-synuclein cytotoxicity during Parkinson's disease". The EMBO Journal. 32 (23): 3041-54. doi:10.1038/ ...
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 ... Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that regulates ... The human alpha-synuclein protein is made of 140 amino acids. An alpha-synuclein fragment, known as the non-Abeta component ( ...
How alpha-Synuclein causes Parkinsons-Associated Neural Damage How alpha-Synuclein causes Parkinsons-Associated Neural Damage ... In Parkinsons disease, alpha-synuclein aggregates released from neurons activate immune cells known as microglia, leading to ... New research, funded in part by NIEHS, has revealed key insights into how alpha-synuclein aggregates cause damage to neurons in ... They also studied why microglia migrate toward injured neurons and tend to accumulate with alpha-synuclein aggregates in the ...
"Cellular milieu imparts distinct pathological {alpha}-synuclein strains in {alpha}-synucleinopathies," by Chao Peng, Ronald J. ... A. "[alpha]-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B," by Diana G Ferreira, ... C. "{alpha}-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation ... "alpha}-Synuclein promotes dilation of the exocytotic fusion pore," by Todd Logan, Jacob Bendor, Chantal Toupin, Kurt Thorn & ...
The behavior of alpha-synuclein in neurons.. Fortin DL1, Nemani VM, Nakamura K, Edwards RH. ... alpha-Synuclein localizes to the nerve terminal, but biochemical experiments have not revealed a tight association with ... To address the dynamics of the protein in live cells, we have used photobleaching and found that alpha-synuclein exhibits high ... In addition to the presumed role of alpha-synuclein dynamics in synaptic function, changes in its physiological behavior may ...
Dominantly inherited mutations in alpha-synuclein cause Parkinsons disease, but the physiological role of alpha-synuclein ... Alpha-synuclein and cysteine-string protein-alpha (CSPalpha) are abundant synaptic vesicle proteins independently linked to ... transgenic alpha-synuclein ameliorates this inhibition. In preventing neurodegeneration in CSPalpha-deficient mice, alpha- ... Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.. Chandra S1, Gallardo G, Fernández-Chacón R, Schlüter ...
MJFF launched the Ken Griffin Alpha-Synuclein Image Competition to spur a scientific race in pursuit of an alpha-synuclein ... Fox Foundation has long supported the pursuit of an alpha-synuclein PET tracer - in addition to funding alpha-synuclein ... In vivo imaging of alpha-synuclein pathology could be useful as a biomarker for the presence of disease and disease progression ... In 2011, with little activity in the field, MJFF established a public-private Alpha-synuclein Imaging Consortium to begin work ...
... by modulation of glial function following activation by soluble or insoluble modified alpha-synuclein (alpha-syn), a chief ... Nitrated alpha-synuclein-activated microglial profiling for Parkinsons disease.. Reynolds AD1, Glanzer JG, Kadiu I, Ricardo- ... alpha-Syn is nitrated during oxidative stress responses and in its aggregated form, induces inflammatory microglial functions. ... To this end, PD-associated inflammation was modeled by stimulation of microglia with aggregated and nitrated alpha-syn. These ...
The rationale for this project is that a therapeutic antibody against alpha-synuclein will be able to block its harmful effects ... Project Description: Antibodies binding to alpha-synuclein have been selected in cell models. One of them has shown positive ... By antibody engineering we will learn about the importance of the strength of antibody binding to alpha-synuclein, and ... Relevance to Diagnosis/Treatment of Parkinsons Disease: Immunotherapy targeting alpha-synuclein is a new way of treating PD. ...
Rabbit polyclonal Alpha-synuclein antibody validated for ICC/IF and tested in Human and Rat. Referenced in 4 publications. ... Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine ... Synthetic peptide corresponding to Human Alpha-synuclein aa 111-131 (C terminal).. Sequence: GILEDMPVDPDNEAYEMPSEE ... A 6.4 Mb duplication of the a-synuclein locus causing frontotemporal dementia and Parkinsonism: phenotype-genotype correlations ...
Chicken polyclonal Alpha-synuclein antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, Horse, Chicken, Cow, Human ... Protein - Recombinant Human Alpha-synuclein protein aggregate (Active) (ab218819) WB, Functional Studies, SDS-PAGE ... Anti-Alpha-synuclein antibody (ab190376) at 1/2000 dilution + Rat brain crude extract. Predicted band size: 14 kDa. ... Ab190376 staining alpha-synuclein in rat cerebellum tissue sections at 1/3000 dilution (red) and co-stained with rabbit ...
GUEST BLOG: Alpha-synuclein - then and now, with Dr. Alice Lazzarini. This week, A Closer Look has a treat - a special guest ... APDA Parkinsons Research Alpha-synuclein - then and now, with Dr. Alice Lazzarini. ... APDA was a key funding partner in the 1996 study that identified alpha-synuclein as a major genetic contributor to PD, as well ... To support your local Alpha-synuclein - then and now, with Dr. Alice Lazzarini chapter, please click the button below:. DONATE ...
Total alpha-synuclein concentration in CSF and oligomeric/total alpha-synuclein ratio in CSF [ Time Frame: Day 0 ]. *Oligomeric ... The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies. ... and total alpha-synuclein concentration in plasma and oligomeric/total alpha-synuclein ratio in plasma [ Time Frame: Day 0 ]. ... Oligomeric Alpha-synuclein in Multiple System Atrophy (BIOAMS). The safety and scientific validity of this study is the ...
A major component of these inclusions is phosphorylated alpha-synuclein (,i,α,/i,-SYN) protein. There is evidence that ,i,α,/i ... A major component of these inclusions is phosphorylated alpha-synuclein (α-SYN) protein. There is evidence that α-SYN pathology ... K. M. Shannon, A. Keshavarzian, H. B. Dodiya, S. Jakate, and J. H. Kordower, "Is alpha-synuclein in the colon a biomarker for ... M. G. Cersosimo, C. Perandones, F. E. Micheli et al., "Alpha-synuclein immunoreactivity in minor salivary gland biopsies of ...
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 ...
Alpha-synucleinUniRule annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, ... tr,A0A2I3N0Z9,A0A2I3N0Z9_PAPAN Alpha-synuclein OS=Papio anubis OX=9555 GN=SNCA PE=3 SV=1 ... Belongs to the synuclein family.UniRule annotation. Automatic assertion according to rulesi ...
2009) Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem ... Templated seeding of alpha-synuclein aggregation. Marija Iljina, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. ... Templated seeding of alpha-synuclein aggregation. Marija Iljina, Gonzalo A. Garcia, Mathew H. Horrocks, Laura Tosatto, Minee L. ... 2008) alpha-Synuclein gene duplication is present in sporadic Parkinson disease. Neurology 70(1):43-49. ...
Blood Plasma of Patients with Parkinsons Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity. Peng Wang,1,2 Xin Li ... This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its ...
2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34:521 ... 2003) Alpha-synuclein pathology affecting Bergmann glia of the cerebellum in patients with alpha-synucleinopathies. Acta ... Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain. Weili Yang, Guohao Wang, Chuan-En Wang, Xiangyu Guo ... Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain. Weili Yang, Guohao Wang, Chuan-En Wang, Xiangyu Guo ...
Alpha-Synuclein Detection. Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult ... Alpha-synuclein (C‑terminus). 18671A, B. IHC. WB. Human. (S122). Rabbit IgG. Cross‑reacts with mouse and rat alpha-synuclein. ... ELISAs for Alpha-Synuclein Detection. The human alpha-synuclein assay kit (Cat. # 27740A) is a solid-phase sandwich ELISA using ... Antibodies for Alpha-Synuclein Detection. Anti-human alpha-synuclein antibody (Cat. # 18671A, B) is an affinity-purified IgG ...
Targeting alpha-synuclein in the gut may slow down Parkinsons disease. Aggregates of the protein alpha-synuclein arising in ... is caused by the buildup of alpha-synuclein proteins in the brain. The biological function of alpha-synuclein is still not ... ... Research by University at Buffalo biologists is providing new insights into alpha-synuclein, a small acidic protein associated ... are associated with the accumulation of alpha-synuclein proteins in the brain. Researchers at the German Center for ...
Invitrogen Anti-alpha Synuclein Recombinant Polyclonal (14HCLC), Catalog # 710110. Tested in Western Blot (WB), ... Mutation of the alpha-synuclein gene is associated with familial forms of PD. Alpha-Synuclein is known to reduce the ... Alpha-Synuclein is involved in the formation of SNARE complexes, and most significantly, aggregated alpha-synuclein is one of ... Alpha-Synuclein belongs to the Synuclein family, which includes beta and gamma Synuclein, and is predominantly expressed in ...
Member of the synuclein family of soluble proteins (alpha-synuclein, beta-synuclein and gamma-synuclein) that are commonly ... Alpha-synuclein. Author: Meenakshi Vij Gupta, M.D. (see Authors page). Revised: 23 May 2016, last major update May 2016. ... Both the sporadic and the familial form of Alzheimer disease also demonstrate alpha-synuclein protein * In recent years, ... several studies have shown that alpha-synuclein aggregation can also be detected outside the central nervous system, ...
Data from 304 PD patients followed for up to eight years indicate that patients with higher cerebrospinal fluid alpha-synuclein ... although no associations were found between alpha-synuclein levels and motor changes. The results are published in the American ... "The finding that alpha-synuclein levels decrease as PD progresses, yet those with higher alpha-synuclein levels experience ... Although several large studies have shown that alpha-synuclein levels are lower in the CSF of PD patients and those with ...
In Parkinsons disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, ... "High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors." Int. J. Mol. Sci. 18, no. 3: 478. ... In Parkinsons disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, ... High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors. Jordi Pujols 1. ...
Aggregation of alpha-synuclein protein in human blood plasma/serum. See Bachelor projects. Aggregation of alpha-synuclein ... coacervatenDetection and quantification of alpha-synuclein aggregates in human blood plasma/serumAggregation of alpha-synuclein ... Aggregation of alpha-synuclein protein in human blood plasma/serum BACHELOR project and MASTER project (published Januari 2019) ... of the protein alpha-synuclein (aSyn), which suggests that aSyn plays an important role in the pathogenesis of PD. In addition ...
Rabbit Polyclonal Anti-alpha-Synuclein Antibody. Validated: WB, ICC/IF, IHC, IHC-Fr, IHC-P. Tested Reactivity: Human, Mouse, ... Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly ... alpha-Synuclein Antibody [NBP2-15365] - Frozen sectioned E13.5 Rat brain. Green: alpha Synuclein protein stained by alpha ... FAQs for alpha-Synuclein Antibody (NBP2-15365). (Showing 1 - 1 of 1 FAQs).. * Im looking for an alpha-Synuclein antibody with ...
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- ...
Anti alpha synuclein Hi people, I purchased an anti- alpha synuclein antibody and I want to try it but I would like to use some ... Home/ Forums/ Antibody Based Technologies: Monoclonal & Polyclonal Antibodies/ Anti alpha synuclein. Anti alpha synuclein. 3 ... What do you recommend me? Do undifferentiated pc12 cells express alpha synuclein? What other cells could I use?. Thank you! ... We carry postive controls for alpha synuclein antibodies please shoot me a PM if your interested in touch. ...
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 ...
Invitrogen Anti-alpha Synuclein Monoclonal (syn211), Catalog # MA5-12272. Tested in Western Blot (WB), Immunofluorescence (IF ... Mutation of the alpha-synuclein gene is associated with familial forms of PD. Alpha-Synuclein is known to reduce the ... Cite alpha Synuclein Monoclonal Antibody (syn211). The following antibody was used in this experiment: alpha Synuclein ... Alpha-Synuclein is involved in the formation of SNARE complexes, and most significantly, aggregated alpha-synuclein is one of ...
  • Alpha-synuclein in solution is considered to be an intrinsically disordered protein, i.e. it lacks a single stable 3D structure. (wikipedia.org)
  • Alpha-synuclein in solution is considered to be an intrinsically disordered protein and thus lacks a stable secondary or tertiary structure. (acris-antibodies.com)
  • Alpha-Synuclein (aSyn) is a 140 amino acid, intrinsically disordered protein that adopts an extended amphipathic alpha-helical structure upon binding the membrane. (umn.edu)
  • Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. (wikipedia.org)
  • 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. (clontech.com)
  • Genomic triplication of the alpha-synuclein gene (SNCA) has been reported to cause hereditary early-onset parkinsonism with dementia. (nih.gov)
  • The A53T mutation in the SNCA gene has been linked to early-onset Parkinson's disease (PD), making this model useful for understanding alpha-synuclein biology and PD pathogenesis. (horizondiscovery.com)
  • Alpha-synuclein (SNCA), an abundantly expressed presynaptic protein, is implicated in Parkinson's disease (PD). (luriechildrens.org)
  • LS-F1634 is a 96-well enzyme-linked immunosorbent assay (ELISA) for the Qualitative detection of Human SNCA / Alpha-Synuclein in samples of Adherent Cell Cultures. (lsbio.com)
  • Addgene: Age-dependent accumulation of oligomeric SNCA/alpha-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA). (addgene.org)
  • 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. (researchmoz.us)
  • The report provides comprehensive information on the Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) , targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchmoz.us)
  • Additionally, the report provides an overview of key players involved in Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA) targeted therapeutics development and features dormant and discontinued projects. (researchmoz.us)
  • Substitution mutations in the SNCA gene encoding alpha-synuclein are the most common cause of familial disease and alpha-synuclein also comprises the principal component of Lewy bodies. (edu.au)
  • Alpha-synuclein also known as SNCA is a protein that, in humans, is encoded by the SNCA gene. (drugster.info)
  • SNCA: a member of the synuclein family. (mybiosource.com)
  • SNCA belongs to the synuclein family, which also includes beta- and gamma-synuclein. (mybiosource.com)
  • alpha Synuclein antibody was raised in Mouse using a purified recombinant fragment of SNCA expressed in E Coli as the immunogen. (mybiosource.com)
  • The report analyses the pipeline products from therapy areas Central Nervous System, Metabolic Disorders, Gastrointestinal, Genetic Disorders, Infectious Disease and Ophthalmology under development targeting Alpha Synuclein (Non A Beta Component Of AD Amyloid or Non A4 Component Of Amyloid Precursor or NACP or SNCA). (globalmarketsdirect.com)
  • New research, funded in part by NIEHS, has revealed key insights into how alpha-synuclein aggregates cause damage to neurons in diseases such as Parkinson's disease. (nih.gov)
  • In Parkinson's disease, alpha-synuclein aggregates released from neurons activate immune cells known as microglia, leading to chronic neuroinflammation that damages neurons. (nih.gov)
  • They also studied why microglia migrate toward injured neurons and tend to accumulate with alpha-synuclein aggregates in the affected areas of Parkinson's disease brains, such as the substantia nigra. (nih.gov)
  • In addition to the presumed role of alpha-synuclein dynamics in synaptic function, changes in its physiological behavior may underlie the pathological changes associated with Parkinson's disease. (nih.gov)
  • Dominantly inherited mutations in alpha-synuclein cause Parkinson's disease, but the physiological role of alpha-synuclein remains unknown. (nih.gov)
  • The ability to image alpha-synuclein deposition in the brain would be a game-changing achievement for the Parkinson's disease field. (michaeljfox.org)
  • Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. (nih.gov)
  • The protein alpha-synuclein is believed to play a major role in the development of Parkinson's disease (PD). (michaeljfox.org)
  • Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). (michaeljfox.org)
  • Growing experimental evidence suggests that the pathological spreading of alpha-synuclein aggregates in Parkinson's disease is mediated through a process of templated seeding whereby aggregates catalyze the conversion of soluble protein molecules into their aggregated forms. (pnas.org)
  • Alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions, such as Parkinson's disease, Lewy body dementia (associated with both Alzheimer's and Parkinson's disease), and multiple system atrophy. (clontech.com)
  • Research by University at Buffalo biologists is providing new insights into alpha-synuclein, a small acidic protein associated with Parkinson's disease. (medicalxpress.com)
  • Aggregates of the protein alpha-synuclein arising in the gut may play a key role in the development of Parkinson's disease (PD). (medicalxpress.com)
  • Parkinson's disease, a neurodegenerative disorder that affects more than 6 million people worldwide, is caused by the buildup of alpha-synuclein proteins in the brain. (medicalxpress.com)
  • Alpha-Synuclein is involved in the formation of SNARE complexes, and most significantly, aggregated alpha-synuclein is one of the major components found in the Lewy bodies that occur in Parkinson's disease (PD) and other neurodegenerative disorders. (thermofisher.com)
  • The antibody specific for alpha-synuclein does not cross react with beta-synuclein and will be useful for the confirmation of Parkinson's disease and Lewy body dementia and other studies for the localization and detection of alpha-synuclein. (thermofisher.com)
  • In Parkinson's disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. (mdpi.com)
  • IHC staining of α-synuclein deposits with purified anti-α-Synuclein, C-Terminal Truncated antibody (clone A15127A) on formalin-fixed, paraffin-embedded Parkinson's disease brain tissue. (biolegend.com)
  • A Nature Neuroscience study reveals the normal role of alpha-synuclein, a protein implicated in Parkinson's disease. (neurosciencenews.com)
  • Researchers report T cells in Parkinson's disease patients respond to alpha synuclein to a greater degree than those without the disease. (neurosciencenews.com)
  • Researchers have implicated an enzyme that appears to make both Tau and alpha synculein more toxic in Alzheimer's and Parkinson's disease. (neurosciencenews.com)
  • Parkinson's disease is characterized by the presence of Lewy-bodies, which primarily contain the protein alpha-synuclein. (uoguelph.ca)
  • She demonstrates that a single alpha-synuclein mutation can elicit the accumulation and aggregation of proteins, characteristic of Parkinson's disease. (uoguelph.ca)
  • Increasing evidence points to inflammation as a chief mediator of Parkinson's disease (PD), a progressive neurodegenerative disorder characterized by loss of dopamine neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein α-synuclein (α-syn). (jneurosci.org)
  • SIGNIFICANCE STATEMENT The main feature associated with Parkinson's disease (PD) is the accumulation of α-synuclein in the brain accompanied by signs of inflammation and immune activation. (jneurosci.org)
  • Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the progressive loss of dopamine-producing neurons in the substantia nigra pars compacta (SNpc) along with widespread intracellular aggregates of the protein α-synuclein (α-syn). (jneurosci.org)
  • Scientists believe that in Parkinson's disease the protein alpha-synuclein changes shape, forming oligomers that aggregate and cause brain cell dysfunction and cell death. (prnewswire.com)
  • There are currently no drugs available that can stop the toxic effects of alpha-synuclein oligomers on brain cells and slow or stop the progression of Parkinson's disease. (prnewswire.com)
  • With this MJFF award, the company will pursue discovery and development of a new generation of compounds active against alpha-synuclein to unlock the potential of its platform for discovering drugs for Parkinson's disease. (prnewswire.com)
  • In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. (nii.ac.jp)
  • a-synuclein has been suggested to be implicated in the pathogenesis of Parkinson's disease and related neurodegenerative disorders, and more recently, to be an important regulatory component of vesicular transport in neuronal cells. (prospecbio.com)
  • A-Synuclein A53T Human Recombinant which is a Parkinson's disease-related point mutant, produced in E.Coli is a single, non-glycosylated polypeptide chain of 140 amino acids having a molecular mass of 14.4kDa (molecular size on SDS-PAGE will appear higher). (prospecbio.com)
  • In parallel, we studied the impact of blood contamination on the detectability of alpha-synuclein (aSyn), a highly abundant protein in blood/erythrocytes and a potential biomarker for Parkinson's disease. (mdpi.com)
  • Alpha-synuclein forms abnormal protein deposits in dopamine neurons and is believed to cause the death of brain cells, leading to Parkinson's Disease. (clinicaltrials.gov)
  • ABSTRACT - A missense G209A mutation of the alpha-synuclein gene was recently described in a large Contursi kindred with Parkinson's disease (PD). (scielo.br)
  • KEY WORDS: Parkinson's disease, alpha-synuclein, genetics. (scielo.br)
  • Parkinson's disease (PD) is the most common movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of proteinacious aggregates enriched in Alpha-Synuclein called Lewy bodies. (ufl.edu)
  • The goals of this Penn U19 "Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias" at the University of Pennsylvania (Penn) Perelman School of Medicine (PSOM) are to elucidate mechanisms of progressive neurodegeneration and dementia in AD +alpha-Synuclein (AD+aSyn), Parkinson's disease (PD), Parkinson's disease with dementia (PDD), dementia with lewy bodies (DLB), and multiple system atrophy (MSA). (upenn.edu)
  • The aggregation of alpha-synuclein (alpha Syn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. (diva-portal.org)
  • Aggregated alpha-synuclein is the main component of Lewy bodies and Lewy neurites, intraneuronal inclusions found in the brains of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) patients (synucleinopathies). (diva-portal.org)
  • This model provides insights into the function of α-synuclein and tau in Parkinson's disease pathogenesis and raises the possibility that this role that may also be conserved in Alzheimer's disease. (dovepress.com)
  • The molecular hallmark of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are megadalton alpha-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. (epfl.ch)
  • Glial alpha-synuclein (alpha-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal alpha-SYN inclusions are found in Parkinson's disease and dementia with Lewy bodies(2). (epfl.ch)
  • Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson's disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. (preprints.org)
  • α-Synuclein has been linked to the pathogenesis of Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. (quanterix.com)
  • Brain alpha-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation. (sysy.com)
  • Aggregated α-synuclein and the point mutations Ala30Pro and Ala53Thr of α-synuclein are associated with Parkinson's disease. (ku.edu)
  • Pathological findings in a patient with alpha-synuclein p.A53T and familial Parkinson's disease. (physiciansweekly.com)
  • The present report documents a patient harboring an alpha-synuclein p.A53T variant from a family presenting with autosomal dominant inheritance, including four patients clinically diagnosed with Parkinson's disease (PD) and two with dementia. (physiciansweekly.com)
  • Alpha-Synuclein has been linked to autosomal dominant early onset Parkinson's Disease (PD). (rpeptide.com)
  • Alpha Synuclein fibrils are prevalent in lewy bodies, a physiological symptom of Parkinson's disease. (rpeptide.com)
  • alpha-Synuclein (alphaS) is a 14.5 kDa neuronal protein associated with Parkinson's disease (PD) and related disorders. (lancs.ac.uk)
  • The deposition of α -synuclein (α -syn) aggregates is a neuropathological feature of Parkinson's disease. (ovid.com)
  • While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. (ijbs.com)
  • α-Synuclein is a pre-synaptic protein whose abnormal aggregation is the main characteristic of a sub-group of neurodegenerative disorders called α-synucleinopathies, including but not limited to Parkinson's disease (PD) and dementia with Lewy bodies (DLB). (bioclinica.com)
  • The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. (drugster.info)
  • A point mutation in the gene coding for the alpha-synuclein protein was the first discovery linking this protein to a rare familial form of Parkinson's disease (PD). (biomol.com)
  • Mutations in alpha-synuclein are strongly linked to development of Parkinson's disease. (thefreedictionary.com)
  • alpha-Synuclein phosphorylation as a therapeutic target in Parkinson's disease. (thefreedictionary.com)
  • alpha-Synuclein (alpha-Syn) is a presynaptic protein implicated in Parkinson's disease (PD). (semanticscholar.org)
  • In this project we assembled a cohort of complementary skills and combined our longterm research programmes to carry out an interdisciplinary study of the structural bases of the toxicity of prefibrilar alpha-synuclein oligomers in view of the crucial interaction with the membrane, which represents the key step in the aetiology of Parkinson's disease. (neurodegenerationresearch.eu)
  • The etiology of Parkinson's disease (PD) is stochastic: a culmination of aging-related changes in brain environment, genetic predispositions, and environmental insults that result in accumulation of alpha-synuclein (α-syn) inclusions (i.e. (biomedcentral.com)
  • Interest in the synuclein family began when alpha-synuclein was found to be mutated in several families with autosomal dominant Parkinson's disease. (wikipedia.org)
  • Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally in Parkinson's disease, Alzheimer's disease, Lewy body disease, and other neurodegenerative diseases. (wikipedia.org)
  • In the brain, alpha-synuclein is found mainly at the tips of neurons in specialized structures called presynaptic terminals. (wikipedia.org)
  • It has been established that alpha-synuclein is extensively localized in the nucleus of mammalian brain neurons, suggesting a role of alpha-synuclein in the nucleus. (wikipedia.org)
  • Synuclein is however found predominantly in the presynaptic termini, in both free or membrane-bound forms, with roughly 15% of synuclein being membrane-bound in any moment in neurons. (wikipedia.org)
  • Thus, it is suggested that alpha-synuclein in mitochondria is differentially expressed in different brain regions and the background levels of mitochondrial alpha-synuclein may be a potential factor affecting mitochondrial function and predisposing some neurons to degeneration. (wikipedia.org)
  • The behavior of alpha-synuclein in neurons. (nih.gov)
  • This can occur, in part, by modulation of glial function following activation by soluble or insoluble modified alpha-synuclein (alpha-syn), a chief component of Lewy bodies that is released from affected dopaminergic neurons. (nih.gov)
  • Alpha-Synuclein belongs to the Synuclein family, which includes beta and gamma Synuclein, and is predominantly expressed in neurons, and concentrated at synaptic terminals. (thermofisher.com)
  • A characteristic pathological feature of PD is the presence of Lewy bodies, which are formed by intracellular deposits of the protein alpha-synuclein in neurons. (eurekalert.org)
  • This may allow damaged or degenerating neurons to maintain their function for longer than those who are less efficient at retaining alpha-synuclein. (eurekalert.org)
  • Immunocytochemistry/ Immunofluorescence: alpha-Synuclein Antibody [NBP2-15365] - DIV14 rat E18 primary cortical neurons were fixed in 4% paraformaldehyde at RT for 15 min. (novusbio.com)
  • alpha-synuclein pathology affects mitochondrial function but is widespread in PD brain, raising the question of its role in the greater vulnerability of nigrostriatal neurons in PD. (sigmaaldrich.com)
  • Thus, in mice over-expressing alpha-synuclein, mitochondrial dysfunction occurred preferentially in nigrostriatal dopaminergic neurons many months before striatal dopamine loss occurs at 14months of age. (sigmaaldrich.com)
  • Alpha-synuclein transfers from neurons to oligodendrocytes. (lu.se)
  • For instance, paraquat and rotenone induce Alpha-Syn up-regulation and aggregation, and elicit loss of dopaminergic neurons in mice and rats respectively. (ufl.edu)
  • Alpha-Synuclein (ASYN) is a protein that is abundant in the human brain and is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. (unl.edu)
  • α-Synuclein has been found concentrated in the presynaptic nerve terminals of neurons and in the nucleus of neurons. (quanterix.com)
  • Lewy bodies are formed by a protein inside neurons called alpha-synuclein. (msfhr.org)
  • MSA is a unique proteinopathy in which alpha-synuclein (α-syn) accumulates preferentially in oligodendroglia rather than neurons. (lu.se)
  • Interestingly, concomitant overexpression of normal TDP-43 and mutant α-synuclein caused a more severe loss of dopaminergic neurons in the double transgenic mice as compared to single-gene transgenic mice. (ijbs.com)
  • TDP-43 potentiated α-synuclein toxicity to dopaminergic neurons in living animals. (ijbs.com)
  • Results within this thesis demonstrate that wild-type alphasynuclein protects both cortical and dopaminergic neurons from oxidative stress. (edu.au)
  • Rather mutant (A53T) alpha-synuclein was linked to sensitisation of neurons through a toxic gain of function which was independent of mitochondrial free-radical production or calcium buffering. (edu.au)
  • Chapter 3 appears to be the equivalent of the post-print version of an article published as: Musgrove RE, King AE, Dickson TC (2011) Neuroprotective upregulation of endogenous alpha-synuclein precedes ubiquitination in cultured dopaminergic neurons, Neurotoxicity research, 19(4), 592-602. (edu.au)
  • Chapter 4 appears to be the equivalent of the post-print version of an article published as: Musgrove RE, King AE, Dickson TC (2013) α-synuclein protects neurons from apoptosis downstream from free radical production through modulation of the MAPK signaling pathway, Neurotoxicity research, 23(4), 358-369. (edu.au)
  • Mice overexpressing human wildtype (WT) alpha-Syn under the Thy1 promoter show high levels of alpha-Syn in cortical and subcortical regions, exhibit progressive sensorimotor anomalies, as well as non-motor abnormalities and are considered models of pre-manifest PD as there is little evidence of early loss of dopaminergic (DA) neurons. (semanticscholar.org)
  • a-synuclein can also be secreted by neurons via exocytosis and can be taken up from neighboring neurons via endocytosis, contributing to the progression of disease pathology.Several studies have demonstrated, that dopaminergic neurons derived from human iPSCs were able to recapitulate some of the defects observed in PD patients, as for example increased susceptibility to oxidative stress or reduced neurite complexity. (fnr.lu)
  • Interestingly, a beneficial role of astrocytes has been shown in a rat model of amyotrophic lateral sclerosis, in which transplantation of wild-type astrocyte precursors lead to a substantial extension of motor neuron survival.Therefore, we aim to analyze the effect of a-synuclein on human astrocytes and on their interplay with dopaminergic neurons. (fnr.lu)
  • We will then analyze whether these different a-synuclein variants can be taken up by astrocytes and neurons and their effects on cellular phenotypes. (fnr.lu)
  • In this context, it will also be interesting to analyze, whether the co-culture of mature healthy astrocytes with healthy or diseased dopaminergic neurons has any beneficial effect on these neurons after a-synuclein treatment. (fnr.lu)
  • A modified form of the alpha-synuclein protein within affected neurons may cause MSA. (wikipedia.org)
  • The rationale for this project is that a therapeutic antibody against alpha-synuclein will be able to block its harmful effects, clearing this protein, and thereby preventing the disease from spreading. (michaeljfox.org)
  • The selected antibody will be optimized using antibody engineering techniques to increase its ability to bind and remove alpha-synuclein. (michaeljfox.org)
  • In order to translate the model studies into the clinic, we will develop assays to evaluate both antibody levels and alpha-synuclein levels in tissues, blood and spinal fluid. (michaeljfox.org)
  • By antibody engineering we will learn about the importance of the strength of antibody binding to alpha-synuclein, and interaction between the antibody and the patient's immune system. (michaeljfox.org)
  • The aim of this study was to test the ability of a therapeutic antibody -- a protein that sticks to alpha-synuclein -- to block alpha-synuclein's harmful effects, remove it from the brain and thereby prevent the spread of PD. (michaeljfox.org)
  • In this study, we first developed an antibody to alpha-synuclein and confirmed its efficacy in alpha-synuclein models of Parkinson's. (michaeljfox.org)
  • Anti-human alpha-synuclein antibody (Cat. (clontech.com)
  • 18671A, B) is an affinity-purified IgG antibody that recognizes human alpha-synuclein protein. (clontech.com)
  • The antibody was raised in rabbit using a synthetic peptide, and can be used for Western blot (WB) detection or immunohistochemical (IHC) detection of human alpha-synuclein protein. (clontech.com)
  • The following antibody was used in this experiment: alpha Synuclein Recombinant Polyclonal Antibody (14HCLC) from Thermo Fisher Scientific, catalog # 710110, RRID AB_2532568. (thermofisher.com)
  • Immunohistochemistry-Frozen: alpha-Synuclein Antibody [NBP2-15365] - Frozen-sectioned adult mouse hippocampus. (novusbio.com)
  • Green: alpha Synuclein protein stained by alpha Synuclein antibody diluted at 1:250. (novusbio.com)
  • Immunohistochemistry-Paraffin: Synuclein-alpha Antibody [NBP2-15365] - Paraffin-embedded Colon ca, using antibody at 1:250 dilution. (novusbio.com)
  • Immunohistochemistry-Paraffin: Synuclein-alpha Antibody [NBP2-15365] - Paraffin-embedded Rat brain diluted at 1:500. (novusbio.com)
  • Immunohistochemistry-Paraffin: Synuclein-alpha Antibody [NBP2-15365] - Paraffin-embedded rat brain. (novusbio.com)
  • Green: alpha Synuclein antibody diluted at 1:200. (novusbio.com)
  • Immunohistochemistry-Frozen: alpha-Synuclein Antibody [NBP2-15365] - Frozen sectioned E13.5 Rat brain. (novusbio.com)
  • Direct ELISA of purified anti-α-Synuclein Phospho (Tyr39) antibody (clone A15119B) binding to plate-immobilized recombinant human unmodified and pY39 and pY125 α-synuclein proteins. (biolegend.com)
  • Western blot of purified anti-α-Synuclein, 80-96 antibody (clone A15115A), and isotype-matched IgG1 control, demonstrating the binding specificity of clone A15115A to endogenous and recombinant human α-synuclein. (biolegend.com)
  • Direct ELISA of purified anti-α-Synuclein, C-Terminal Truncated antibody (clone A15127A) binding to plate-immobilized recombinant human full-length (1-140) and C-terminally fragmented (1-122) α-synuclein. (biolegend.com)
  • IHC staining of purified anti-α-Synuclein Phospho (Ser129) antibody (clone P-syn/81A) on formalin-fixed paraffin-embedded diseased human brain tissue. (biolegend.com)
  • Western blot of anti-α-Synuclein antibody (clone A15126D) and isotype-matched IgG2b control, binding to endogenous and recombinant human α-synuclein. (biolegend.com)
  • Hi people, I purchased an anti- alpha synuclein antibody and I want to try it but I would like to use some positive control. (scientistsolutions.com)
  • The following antibody was used in this experiment: alpha Synuclein Monoclonal Antibody (syn211) from Thermo Fisher Scientific, catalog # MA5-12272, RRID AB_10978319. (thermofisher.com)
  • The invention provides methods of detecting alpha-synuclein using a capture antibody and a reporter antibody. (wipo.int)
  • The capture antibody binds preferentially to full-length alpha- synuclein phosphorylated at residue 129 (PS129 alpha-synuclein) over unphosphorylated full- length alpha-synuclein. (wipo.int)
  • The reporter antibody binds to an epitope within residues 40-55 of alpha-synuclein. (wipo.int)
  • The recombinant human synuclein family (α-, β-and γ-) and α-synuclein domains (1-60, 1-95, 61-140 and 96-140) proteins were resolved by SDS-PAGE, transferred to PVDF membrane and probed with anti-α-Synuclein (61-95 aa) antibody Cat. (acris-antibodies.com)
  • Synuclein-alpha (Phospho-Tyr136) Antibody detects endogenous levels of Synuclein-alpha only when phosphorylated at Tyr136. (avivasysbio.com)
  • LB are largely composed of fibrillar aggregates (amyloid) of the protein alpha-synuclein (aSyn), which suggests that aSyn plays an important role in the pathogenesis of PD. (utwente.nl)
  • LB are largely composed of fibrillar aggregates (amyloid) of the protein alpha-synuclein (aSyn). (utwente.nl)
  • The natively unstructured, membrane-bound protein $\alpha $-synuclein is thought to play a role in vesicle trafficking. (aps.org)
  • 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)
  • 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)
  • Parkinsons disease and other alpha-synucleinopathies are progressive neurodegenerative diseases characterized by aggregates of misfolded alpha-synuclein spreading throughout the brain. (diva-portal.org)
  • The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. (rsc.org)
  • The protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. (rcsb.org)
  • The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. (preprints.org)
  • BACKGROUND: The formation of alpha-synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). (surrey.ac.uk)
  • In fact, alpha-synuclein aggregates are the main constituent of Lewy Bodies, characteristic proteins inclusions found in parkinsonian brains. (thefreedictionary.com)
  • One of the major hallmarks of PD is the formation of so called Lewy Bodies, protein aggregates that primarily consist of a-synuclein. (fnr.lu)
  • Within these structures, alpha-synuclein interacts with phospholipids and proteins. (wikipedia.org)
  • Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, making up as much as 1% of all proteins in the cytosol of brain cells. (wikipedia.org)
  • Alpha-synuclein and cysteine-string protein-alpha (CSPalpha) are abundant synaptic vesicle proteins independently linked to neurodegeneration. (nih.gov)
  • These observations reveal a powerful in vivo activity of alpha-synuclein in protecting nerve terminals against injury and suggest that this activity operates in conjunction with CSPalpha and SNARE proteins on the presynaptic membrane interface. (nih.gov)
  • Parkinson's and multisystem atrophy (MSA), both neurodegenerative diseases, are associated with the accumulation of alpha-synuclein proteins in the brain. (medicalxpress.com)
  • Synucleins are a family of small and soluble proteins expressed mostly in neural tissue and cancer cells. (intechopen.com)
  • Lewy bodies are composed of truncated and phosphorylated intermediate neurofilament proteins, alpha synuclein, ubiquitin and associated enzymes. (genetex.com)
  • The synuclein phosphoproteins (15-20 kD) are small highly conserved proteins in vertebrates. (genetex.com)
  • Thereofore, research must be continued in order to better understand the functions of the synuclein proteins under normal physiological conditions as well as their role in disease. (omicsonline.org)
  • Alpha-Synuclein (α- Synuclein) is a member of the synuclein family of proteins including β-synuclein and γ-synuclein. (quanterix.com)
  • TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. (ijbs.com)
  • Our finding provides in vivo evidence suggesting that disease proteins such as TDP-43 and α-synuclein may play a synergistic role in disease induction in neurodegenerative diseases. (ijbs.com)
  • Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors. (wikipedia.org)
  • The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. (wikipedia.org)
  • Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins. (wikipedia.org)
  • Alpha-synuclein InterPro: IPR002460 Beta-synuclein InterPro: IPR002461 Gamma-synuclein InterPro: IPR002462 Normal cellular functions have not been determined for any of the synuclein proteins. (wikipedia.org)
  • The results have highlighted complexities surrounding the contentious role of alpha-synuclein in both neuroprotection and toxicity. (edu.au)
  • Significantly, this twohit hypothesis validates past studies, which have detailed a role of alpha-synuclein in both neuroprotection through chaperone activity, and in neurotoxicity through a toxic gain of function mechanism. (edu.au)
  • A. " Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid {alpha}-synuclein fibrils ," by Francesco Simone Ruggeri, Fabrizio Benedetti, Tuomas P. J. Knowles, Hilal A. Lashuel, Sergey Sekatskii, and Giovanni Dietler (Vol. 115 No. 28, July 10, 2018, p. 7230-7235). (wisc.edu)
  • It is believed that oligomers of $\alpha $-synuclein are the toxic species, whereas sequestration into fibrils is neuroprotective. (aps.org)
  • X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length α-synuclein. (rcsb.org)
  • The NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length α-synuclein fibril, presenting opportunities for the design of inhibitors of α-synuclein fibrils. (rcsb.org)
  • Alpha-synuclein fibrils are major substituent of the intracellular Lewy bodies seen in Parkinson rsquo;s disease. (acris-antibodies.com)
  • We assess the properties of structurally well-defined alpha-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. (epfl.ch)
  • While native α-synuclein is unfolded, it has a propensity to form toxic soluble oligomers (i.e., protofibrils) that ultimately aggregate into insoluble fibrils. (quanterix.com)
  • The fibrils and amyloidal forms of α-synuclein are major components of Lewy bodies. (quanterix.com)
  • In the present study, we investigated the temporal relationship of neuroinflammation in a model of synucleinopathy following intrastriatal injection of pre-formed alpha-synuclein fibrils (α-syn PFFS). (biomedcentral.com)
  • In vivo imaging of alpha-synuclein pathology could be useful as a biomarker for the presence of disease and disease progression and as a pharmacodynamic tool for drug development. (michaeljfox.org)
  • In vivo binding patterns consistent with the expected distribution of alpha-synuclein pathology per population (e.g. (michaeljfox.org)
  • 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)
  • The postmortem examination showed atrophy of the substantia nigra, lack of Alzheimer pathology, and numerous Lewy bodies which were immunoreactive to alpha-synuclein and ubiquitin in cortical and subcortical areas. (nih.gov)
  • Our results demonstrate that distinct alpha-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes. (epfl.ch)
  • A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease. (preprints.org)
  • Alpha-synuclein p.A53T characteristically cause the Lewy body pathology and the symptoms, that resembled those of the reported patients with p.A53T. (physiciansweekly.com)
  • Colonic inflammation, alpha-synuclein pathology in the gut, and dysbiosis of the gut microbiome in PD are among the many clues. (thefreedictionary.com)
  • The formation of unique and filamentous inclusion bodies called Lewy bodies (LBs) is the hallmark of both PD and dementia with LBs. The key pathology in PD is generally considered to be the alpha-synuclein (α-syn) accumulation, although it is still controversial whether this protein aggregation is a cause or consequence of neurodegeneration. (bmbreports.org)
  • 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. (clinicaltrials.gov)
  • Alpha-Synuclein is a small, presynaptic protein that is the major nonamyloid component of the pathological inclusions characteristic of a wide range of neurodegenerative disorders, collectively known as synucleinopathies. (thermofisher.com)
  • Alpha synuclein in neurodegenerative disorders: murderer or accomplice? (wikipedia.org)
  • Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release. (wikipedia.org)
  • It has also been shown that alpha-synuclein is localized in neuronal mitochondria. (wikipedia.org)
  • Indeed, there is growing evidence that alpha-synuclein is involved in the functioning of the neuronal Golgi apparatus and vesicle trafficking. (wikipedia.org)
  • Toxic forms of alpha-synuclein can cause neuronal dysfunction and, when secreted from cells, the protein can be taken up by neighboring cells, thereby spreading the disease from one brain region to another. (michaeljfox.org)
  • The alpha and beta synucleins are found primarily in brain tissue where they are seen mainly in neuronal cytosol and presynaptic terminals. (thermofisher.com)
  • Neuronal α-Synuclein is concentrated in presynaptic nerve terminals, interacts with plasma membrane phospholipids, and is also present in nuclei and mitochondria. (biolegend.com)
  • In the following years, synucleins have been linked with other neuronal disorders increasing the interest of elucidating their connection with these diseases. (intechopen.com)
  • a-Synuclein (amino acids 1-140), an acidic neuronal protein of 140 amino acids, is extremely heat-resistant and is natively unfolded with an extended structure primarily composed of random coils. (prospecbio.com)
  • The presence of alpha-synuclein in blood raises the possibility of using the protein as a marker for disease states and to test the effect of drugs on neuronal activity. (perkinelmer.com)
  • Neuronal accumulation of a protein called alpha synuclein (α-syn) appears to be a critical step in the development of PD and other neurodegenerative diseases, collectively referred to as synucleinopaties. (omicsonline.org)
  • Alpha-synuclein expression was correlated to neuronal health, free radical production, mitochondrial function and metabolism. (edu.au)
  • Data within this thesis also supports a role for alpha-synuclein in facilitating neuronal energy production through oxidative phosphorylation. (edu.au)
  • In contrast to wild-type protein, expression of mutant (A35T) alpha-synuclein increased neuronal susceptibility to oxidative toxicity. (edu.au)
  • In summary, the studies within this thesis have clarified the contribution of alpha-synuclein to normal neuronal function and the mechanisms of PD and DLB. (edu.au)
  • Alpha synuclein is an abundant 140 amino acid neuronal protein, expressed primarily at. (biomol.com)
  • The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. (wikipedia.org)
  • Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. (springer.com)
  • Alpha-synuclein is a presynaptic protein, which is most commonly an unfolded monomer in its physiological state. (diva-portal.org)
  • Alpha-Synuclein (α-Synuclein) is a 14 kD (140 amino acids) acidic presynaptic protein. (rpeptide.com)
  • Snaring the function of alpha-synuclein. (nih.gov)
  • The exact function of alpha-synuclein is unknown, but it may be involved in presynaptic signaling and membrane trafficking. (clontech.com)
  • The physiological function of alpha-synuclein appears to require its translocation between these subcellular compartments and interconversion between the 2 conformations. (biomol.com)
  • Aberrant aggregation of alpha-synuclein has been detected in an increasing number of neurodegenerative diseases, collectively known as synucleopathies. (biomol.com)
  • The accumulation of aggregated alpha-synuclein is a pathological hallmark of Parkinson's and a priority target for drug development given its hypothesized contribution to neurodegeneration. (michaeljfox.org)
  • 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)
  • Similar levels of alpha-synuclein accumulation in mitochondria were detected in the ventral midbrain, striatum and cortex of Thy1-aSyn mice. (sigmaaldrich.com)
  • Synuclein family members (alpha-, beta-, and gamma-synuclein) are expressed at high levels in adult brain tissue and in some tumors. (clontech.com)
  • The synuclein family includes alpha and beta synucleins and loosely related gamma synuclein and synoretin. (genetex.com)
  • Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. (genetex.com)
  • The gamma-synuclein protein's expression in breast tumors is a marker for tumor progression. (wikipedia.org)
  • Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. (nih.gov)
  • Here, we report the surprising finding that transgenic expression of alpha-synuclein abolishes the lethality and neurodegeneration caused by deletion of CSPalpha. (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)
  • A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection. (curehunter.com)
  • Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. (lsbio.com)
  • Here, we evaluate the evidence for and against the role of α-synuclein in destabilizing microtubules, causing axonal transport deficits and eventually neurodegeneration. (dovepress.com)
  • This thesis will provide a basis and direction for further investigations into the relationship between intracellular alpha-synuclein levels, and the selective nature of neurodegeneration in PD and DLB. (edu.au)
  • Conversely, ablation of endogenous synucleins exacerbates these phenotypes. (nih.gov)
  • The resulting model expresses a humanized A53T alpha-synuclein protein without endogenous rat alpha-synuclein. (horizondiscovery.com)
  • Recognizes endogenous levels of Alpha-synuclein (pS129) protein. (genetex.com)
  • Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers. (abcam.com)
  • Using these methods, the company is also testing the effect of drug candidates on the toxic alpha-synuclein oligomers. (prnewswire.com)
  • The oxidative stress-related reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown to promote formation of alpha-synuclein oligomers in vitro. (diva-portal.org)
  • However, ONE-induced alpha-synuclein oligomers exhibited a slightly higher degree of beta-sheet. (diva-portal.org)
  • Moreover, to probe the selective interaction of the two types of oligomers with a variety of lipid membranes, we will adapt our recent approach that successfully unveiled the nature of the interaction between monomeric alpha-synuclein and lipid membranes (Fusco et al, Nature Communications, 2014 5:3827). (neurodegenerationresearch.eu)
  • 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)
  • Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature in MSA. (clinicaltrials.gov)
  • As the impact of this pathological spreading mechanism is currently debated, we aimed to investigate the transfer and subcellular location of alpha-synuclein species in a novel 3D co-culture human cell model based on highly differentiated SH-SY5Y cells. (diva-portal.org)
  • Antibodies to alpha synuclein provide a specific method to detect Lewy bodies and associated pathological mechanism of PD and AD. (genetex.com)
  • Abnormal processing of alpha-synuclein is predicted to lead to pathological changes in its binding properties and function. (biomol.com)
  • Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. (preprints.org)
  • Alpha Synuclein is the major component of Lewy bodies and Lewy neuritis in sporadic PD, dementia with Lewy Bodies and Lewy Body variant of AD. (genetex.com)
  • Studies have focused heavily on the protein α-synuclein, which is the primary component of Lewy bodies, the pathologic inclusions that are the hallmark of Parkinson's on the cellular level. (dovepress.com)
  • alpha-Synuclein protects SH-SY5Y cells from dopamine toxicity. (sysy.com)
  • The structural investigation will be complemented biophysical and cellular toxicity measurements to define the underlying structural bases of cellular toxicity of alpha-synuclein. (neurodegenerationresearch.eu)
  • ELISA was performed by coating wells with 150 ng of each recombinant α-synuclein protein. (biolegend.com)
  • ELISA assays were developed to investigate if parkin interacts with alpha-synuclein in human blood plasma. (lancs.ac.uk)
  • This study documents the analytical performance characteristics of a novel colorimetric ELISA targeting α-Synuclein in biological fluids, with a focus on cerebrospinal fluid (CSF). (bioclinica.com)
  • α-Synuclein concentrations have been determined using a colorimetric ELISA designed and developed by ADx NeuroSciences using two monoclonal antibodies. (bioclinica.com)
  • The newly developed α-Synuclein colorimetric ELISA assay meets all of our internal acceptance criteria for clinical trial sample testing and represents an additional tool for patient enrichment in clinical trials or treatment follow-up. (bioclinica.com)
  • It has been shown that alpha-synuclein is localized in the inner membrane of mitochondria, and that the inhibitory effect of alpha-synuclein on complex I activity of mitochondrial respiratory chain is dose-dependent. (wikipedia.org)
  • It has been shown that alpha-synuclein significantly interacts with tubulin, and that alpha-synuclein may have activity as a potential microtubule-associated protein, like tau. (wikipedia.org)
  • Although several large studies have shown that alpha-synuclein levels are lower in the CSF of PD patients and those with related synucleinopathies compared to controls, its role in cognitive decline and dementia had been unexplored. (eurekalert.org)
  • Knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory. (wikipedia.org)
  • Over-expression of alpha-synuclein in the nervous system enhances axonal degeneration after peripheral nerve lesion in a transgenic mouse strain. (sysy.com)
  • Antibodies binding to alpha-synuclein have been selected in cell models. (michaeljfox.org)
  • At the same time, we designed several other antibodies to alpha-synuclein as additional therapeutic candidates. (michaeljfox.org)
  • We carry postive controls for alpha synuclein antibodies please shoot me a PM if your interested in touch. (scientistsolutions.com)
  • Monoclonal antibodies (mab) are offered that all specifi-cally for human alpha-Synuclein and well characterized regarding their binding to antigen especially their epitope specificity. (analytik-jena.de)
  • The main objectives are to determine on one hand whether oligomeric alpha-synuclein levels are increased in MSA patients compared to controls and on other hand whether there is a good agreement between cerebrospinal fluid (CSF) and plasma levels. (clinicaltrials.gov)
  • Concentration of oligomeric alpha-synuclein in cerebrospinal fluid (CSF). (clinicaltrials.gov)
  • This assay kit is capable of quantitative determination of human alpha-synuclein in serum, EDTA plasma, cerebrospinal fluid (CSF), and cell culture supernatant. (clontech.com)
  • Data from 304 PD patients followed for up to 8 years indicate that patients with higher cerebrospinal fluid (CSF) alpha-synuclein levels experienced faster cognitive decline in the following months, although no associations were found between alpha-synuclein levels and motor changes. (eurekalert.org)
  • The AlphaLISA ® immunoassay kit for human Alpha-synuclein enables the quantitative determination of Alpha-synuclein in biological fluids such as serum, plasma, cerebrospinal fluid and cell culture supernatants using a homogeneous AlphaLISA assay (no wash steps). (perkinelmer.com)
  • Alpha-synuclein is also found in cerebrospinal fluid, which is the fluid surrounding the brain and spinal cord. (msfhr.org)
  • While we know that alpha-synuclein in cerebrospinal fluid is helpful for distinguishing dementia with Lewy bodies from Alzheimer's disease, further work is needed to improve this test. (msfhr.org)
  • This kit has been designed for the detection and quantification of alpha-synuclein in serum, plasma, and cell culture supernatants. (perkinelmer.com)
  • An alpha-synuclein fragment, known as the non-Abeta component (NAC) of Alzheimer's disease amyloid, originally found in an amyloid-enriched fraction, was shown to be a fragment of its precursor protein, NACP. (wikipedia.org)
  • It was later determined that NACP was the human homologue of Torpedo synuclein. (wikipedia.org)
  • Therefore, NACP is now referred to as human alpha-synuclein. (wikipedia.org)
  • The following year, in 1997, we would publish the paper that showed that PARK1 was the protein α-synuclein ). (apdaparkinson.org)
  • The MA5-12272 immunogen is human recombinant alpha-synuclein. (thermofisher.com)
  • We have examined mitochondrial function and oxidative damage in mice overexpressing human wild type alpha-synuclein broadly throughout the nervous system under the Thy1 promoter (Thy1-aSyn mice) between 4 and 8months of age. (sigmaaldrich.com)
  • A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). (springer.com)
  • The implication of alpha synuclein in neurodegenerative diseases started after the identification of non A beta component of amyloid (NAC peptide) in Alzheimeris disease (AD) brains. (genetex.com)
  • An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human α-synuclein. (rcsb.org)
  • The alpha-synuclein G209A mutation assay was made using polymerase chain reaction and the restriction enzyme Tsp45I. (scielo.br)
  • Allele-specific polymerase chain reaction was used for screening of three pathogenic single nucleotide polymorphisms in alpha-synuclein gene. (thefreedictionary.com)
  • Rather than unveiling their physiological properties and functions in normal brain tissue, the synucleins are mostly exploited as biomarkers for neurodegenerative diseases since the discovery of their involvement in proteinaceous aggregation in patients with Alzheimer's disease (AD) [ 1 ]. (intechopen.com)
  • The physiological function of α-synuclein may associate with regulating synaptic transmission, dopamine metabolism, vesicle trafficking etc. (quanterix.com)
  • The physiological roles of α-synuclein and methionine oxidation of the α-synuclein protein structure and function are not fully understood. (ku.edu)
  • Nevertheless, mutations in the alpha-synuclein gene are a rare cause of PD in families from North America, 4,5 Europe 6 and China 7 . (scielo.br)
  • Certain missense mutations in the alpha synuclein gene (A53T, A30P) have been linked to the familial Parkinsonis disease (PD). (genetex.com)
  • Subsequently, other mutations in the alpha-synuclein gene have been identified in familial PD. (biomol.com)
  • The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies. (clinicaltrials.gov)
  • Our data show that, in addition to the previously described hereditary alpha-synucleinopathies, dementia with Lewy bodies is related to mutation of alpha-synuclein. (nih.gov)
  • The association of alpha synuclein (α-Syn) with several progressive disorders has focused the research on its induced conformational behavior as critical for uncovering the "secrets" for progression of α-synucleinopathies. (intechopen.com)
  • There is now a general group of synucleinopathies which implicates alpha synuclein in Lewy body syndromes, Parkinsonis disease, and Alzheimeris disease. (genetex.com)
  • The discovery of alpha-SYN assemblies with different structural characteristics or 'strains' has led to the hypothesis that strains could account for the different clinicopathological traits within synucleinopathies(3,4). (epfl.ch)
  • Thus, a compromised MsrA function combined with α-synuclein overexpression may promote processes leading to synucleinopathies. (ku.edu)
  • A major component of these inclusions is phosphorylated alpha-synuclein ( α -SYN) protein. (hindawi.com)
  • Aggregated protein inclusions called Lewy bodies found in the brain in PD contain alphaS. (lancs.ac.uk)
  • The aggregated proteinaceous inclusions called Lewy bodies found in PD and cortical Lewy body dementia (LBD) were discovered to be predominantly alpha-synuclein. (biomol.com)
  • Mutation of the alpha-synuclein gene is associated with familial forms of PD. (thermofisher.com)
  • Sequencing of the alpha-synuclein gene showed a novel, nonconservative E46K mutation in heterozygosis. (nih.gov)
  • The objective of this study is to determine if the mutation G209A of the alpha-synuclein gene was present in 10 Brazilian families with PD. (scielo.br)
  • Our results suggest that alpha-synuclein mutation G209A is uncommon in Brazilian PD families. (scielo.br)
  • 2 found a missense G209A mutation in the alpha-synuclein gene in a large family diagnosed with PD from Contursi, Italy and in another 3 Greek families with an autossomal dominant pattern. (scielo.br)
  • This point mutation leads to the substitution of alanine by treonine at the 53 position in the aminoacid sequence of the alpha-synuclein (Ala53Thr) 1 . (scielo.br)
  • In Brazil there are no studies focusing on the mutations of the alpha-synuclein in families with PD and our study's objective is to determine whether the G209A mutation can be found among 10 Brazilian families with PD. (scielo.br)
  • The G209A mutation of the alpha-synuclein gene was detected by using the Tsp451 restriction enzyme, as previously described 1 . (scielo.br)
  • We could not find the G209A mutation in the exon 4 of the alpha-synuclein gene in the families studied. (scielo.br)
  • The alpha-synuclein p.A53T variant is linked to young- or middle-aged onset parkinsonism and cognitive decline. (physiciansweekly.com)
  • The Nature study reports four genetic variations are associated with T cell reactivity to alpha synuclein. (neurosciencenews.com)
  • MA5-12272 targets Synuclein in IHC (P), ICC/IF, IP, and WB applications and shows reactivity with Human and Rat samples. (thermofisher.com)
  • Synucleins may be involved in the regulation of dopamine release and transport and the modulation of synaptic vesicle function. (thermofisher.com)
  • Synthetic peptide corresponding to Human Alpha-synuclein aa 111-131 (C terminal). (abcam.com)
  • Recombinant full length protein corresponding to Human Alpha-synuclein aa 1-140. (abcam.com)
  • Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification. (sysy.com)
  • a-Synuclein is also the main component of pathogenic Lewy bodies and Lewy neurites. (biomol.com)
  • She will create a diagnostic tool for clinical use to measure alpha-synuclein, and also explore modifications of alpha-synuclein that occur in disease that could improve our ability to identify dementia with Lewy bodies. (msfhr.org)
  • CFS α-Synuclein levels reflect the presence of Lewy bodies in the brain and have been shown to be decreased in PD and DLB patients as compared to healthy aging controls. (bioclinica.com)
  • Region specific mitochondrial impairment in mice with widespread overexpression of alpha-synuclein. (sigmaaldrich.com)
  • Alpha-synuclein overexpression in mice alters synaptic communication in the corticostriatal pathway. (semanticscholar.org)
  • Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. (genetex.com)
  • The human alpha-synuclein protein is made of 140 amino acids. (wikipedia.org)
  • Moreover, recent studies have shown that a-synuclein has chaperone activity and that this activity is lost upon removing its C-terminal acidic tail (amino acids 96-140). (prospecbio.com)
  • a-Synuclein Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain of 140 amino acids having a molecular mass of 14.4kDa (Real molecular weight on SDS-PAGE will be shift up). (prospecbio.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)
  • Alpha-synuclein is a 140 amino acids protein primarily expressed in the mammalian brain. (perkinelmer.com)
  • While the roles of α-synuclein in causing mitochondrial dysfunction and disruptions to the proteasomal system have been well documented, recently, its role in effecting microtubule dynamics has been investigated as a potential source of pathogenicity. (dovepress.com)
  • The Recombinant Human a-Synuclein is purified by proprietary chromatographic techniques. (prospecbio.com)
  • Recombinant human alpha synuclein, produced in E.coli. (genetex.com)
  • These neurodegenerative multisystem disorders have widespread occurrence of α-synuclein containing deposits in the central, peripheral, and autonomic systems. (pathologyoutlines.com)
  • This is a Phase I clinical trial of phenylbutyrate in 20 Parkinson patients and 20 age- and sex-matched normal control subjects to see if phenylbutyrate can increase the removal of alpha-synuclein from the brain into the bloodstream. (clinicaltrials.gov)
  • Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications. (lsbio.com)
  • Mutations of the a-synuclein gene have been linked to Parkinson disease. (biomol.com)
  • 2006) Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. (thefreedictionary.com)
  • Experimental evidence has been collected on the interaction of alpha-synuclein with membrane and its involvement with membrane composition and turnover. (wikipedia.org)
  • Despite considerable evidence linking alpha-synuclein with membranes in vitro, it has proven difficult to demonstrate membrane association of the protein in vivo. (nih.gov)
  • Alpha-synuclein interacts with plasma membrane phospholipids. (acris-antibodies.com)
  • Alpha-synuclein exists physiologically in both soluble and membrane-bound states, in unstructured and alpha-helical conformations, respectively. (biomol.com)
  • As of 2014, an increasing number of reports suggest, however, the presence of partial structures or mostly structured oligomeric states in the solution structure of alpha-synuclein even in the absence of lipids. (wikipedia.org)
  • Fluorescently-labeled monomeric, oligomeric and fibrillar species of alpha-synuclein were introduced into a donor cell population and co-cultured with an EGFP-expressing acceptor-cell population of differentiated neuron-like cells. (diva-portal.org)
  • Size exclusion chromatography showed that after 1 h of incubation, HNE induced the formation of an oligomeric alpha-synuclein peak with a molecular weight of about similar to 2000 kDa, which coincided with a decreasing similar to 50 kDa monomeric peak. (diva-portal.org)
  • In contrast, peroxiredoxin 2 increased in the striatum and cortex, which may contribute to their protection in the presence of high levels of alpha-synuclein. (sigmaaldrich.com)
  • However, the changes in secondary structure of alpha-synuclein and the kinetics of the oligomerization process are not known and were the focus of this study. (diva-portal.org)
  • Further, neural activity controls the distribution of alpha-synuclein, causing its dispersion from the synapse. (nih.gov)
  • Alpha-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the brain during a period of acquisition-related synaptic rearrangement. (wikipedia.org)
  • He and his colleagues, including first author, Tessandra Stewart, PhD, suggest that the decrease in CSF alpha-synuclein may be the result of a compensatory process, reflecting greater retention of the protein in the brain. (eurekalert.org)
  • This is a Phase I clinical trial of the FDA approved drug Glycerol Phenylbutyrate to see if phenylbutyrate can increase the removal of alpha-synuclein from the brain into the bloodstream. (clinicaltrials.gov)
  • Alpha-synuclein is expressed principally in the central nervous system (brain) but is also expressed in low concentrations in a variety of tissues except liver. (acris-antibodies.com)
  • Alpha Synuclein is a protein of 140aa expressed abundantly in the brain. (biomol.com)
  • Additionally, we show that alpha-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. (epfl.ch)
  • However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. (preprints.org)
  • Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes. (harvard.edu)
  • Excess levels of either calcium or alpha-synuclein may be what starts the chain reaction that leads to the death of brain cells. (thefreedictionary.com)