Synuclein. Medical search. Frequent questions

We here report the structure of cytotoxic alpha-synuclein fibrils (residues 1-121), determined by cryo-electron microscopy at a resolution of 3.4 Å. (nih.gov)
An alteration in Beta-synuclein may impair its normal inhibitory action on the formation of toxic alpha-synuclein fibrils, thereby indirectly contributing to disease pathogenesis (2). (signalchem.com)
Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by microinjection of pre-formed α-synuclein fibrils (PFFs). (biomedcentral.com)
A number of in vitro studies showed that dopamine can modulate the aggregation of α-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils. (elsevierpure.com)
To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures. (barrowneuro.org)
Specifically, alpha-synuclein aggregates (contained in a biological sample) seed the polymerization of vast stoichiometric excesses of recombinant, normally folded alpha-synuclein into amyloid fibrils that are then detectable by an amyloid-sensitive fluorescent dye. (nih.gov)

While the study does not directly address neurodegeneration, the data describe a physiological role for α-synuclein that explains how trapping the protein in Lewy bodies, as in slowly progressive neurodegenerative diseases such as PD, might seem initially harmless but cause neurons to suffer in the long run. (alzforum.org)
The researchers found that α-synuclein sustains waning neurons by helping them make SNARE complexes. (alzforum.org)
Moreover, the authors found that restoring expression of α-synuclein in cultured neurons from the triple knockout mice helped re-establish SNARE complexes, and did so in a dose-dependent way. (alzforum.org)
Although the major aggregating peptide in β-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (αSyn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in β-cells. (nature.com)
Parkinson's disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. (nih.gov)
Taken together we have provided evidence that excessive O-GlcNAcylation is detrimental to neurons by inhibition of autophagy and by increasing α-synuclein accumulation. (biomedcentral.com)
Immunofluorescence microscopy revealed an increase in punctate (lysosomal) LAMP-2A staining that co-localized with α-synuclein within nigral dopaminergic neurons of paraquat-treated and α-synuclein-overexpressing animals. (elsevierpure.com)
Accordingly, by combining electrophysiological, optogenetic, immunofluorescence, molecular and behavioural analyses, here we report that α-synuclein reduces N-methyl-d-aspartate (NMDA) receptor-mediated synaptic currents and impairs corticostriatal long-term potentiation of striatal spiny projection neurons, of both direct (D1-positive) and indirect (putative D2-positive) pathways. (unimi.it)
Conclusion/Significance: Our results show, for the first time, a direct effect of dopamine on the conformation of α-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson's disease. (elsevierpure.com)
Importantly, researchers were able to decrease the activity of TLR2 by inhibiting its interaction with MyD88 via the nasal administration of peptides that correspond to wtTIDM (wild-type TLR2-interacting domain of MyD88) and wtNBD (wild-type NEMO-binding domain), and this decreased interaction reduced the spread of alpha-synuclein and protected dopaminergic neurons in the peptide-treated mice. (cndlifesciences.com)
Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons). (medlineplus.gov)
Direct transmission of alpha-synuclein from pathologically affected to healthy unaffected neurons may be important in the anatomical spread of the disease through the nervous system. (ox.ac.uk)
By contrast, α-synuclein - deficient neurons, which cannot form α-synuclein aggregates, failed to exhibit either oxidative stress or c-Abl activation. (barrowneuro.org)
N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism, suppressed the PFF - induced redox stress and c-Abl activation in the wild-type neurons, and likewise suppressed α-synuclein aggregation. (barrowneuro.org)
In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. (nih.gov)
Alpha-synuclein (red) in the neurons of the appendix. (nih.gov)

Heat shock proteins reduce alpha-synuclein aggregation induced by MPP+ in SK-N-SH cells. (nih.gov)
The aggregation and fibrillation of α-synuclein has been implicated as a causative factor in the disease, and the process of fibril formation has been intensively studied in vitro with dilute protein solutions. (usf.edu)
β-Synuclein (β-syn) can counteract α-syn aggregation. (nih.gov)
These interactions are considered critical for at least some normal functions of alpha-synuclein, and may well play critical roles in both the aggregation of the protein and its mechanisms of toxicity. (en-journal.org)
Alpha synuclein's contribution to such disorders could in principle result either from a toxic gain of function resulting from synuclein oligomerization and/or aggregation, or from a loss or perturbation of normal synuclein function (or possibly from a combination of the two). (en-journal.org)
The processes of aggregation and spreading of α-synuclein were thereby shown to be independent of phosphorylation at serine-129. (biomedcentral.com)
Background: Oligomerization and aggregation of α-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease. (elsevierpure.com)
However, α-synuclein oligomerization and aggregation have mostly been detected indirectly in cells using detergent extraction methods. (elsevierpure.com)
Brown JW, Buell AK, Michaels TC, Meisl G, Carozza J, Flagmeier P, Vendruscolo M, Knowles TP, Dobson CM, Galvagnion C. beta-Synuclein suppresses both the initiation and amplification steps of alpha-synuclein aggregation via competitive binding to surfaces. (medlineplus.gov)
Alpha-synuclein aggregation plays a central role in Parkinson's disease pathology. (ox.ac.uk)
Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. (barrowneuro.org)
Parallel findings were observed in mouse brain: PFF-induced α-synuclein aggregation in the substantia nigra was associated with redox stress, c-Abl activation, and dopaminergic neuronal loss, along with microglial activation and motor impairment, all of which were attenuated with oral N-acetyl cysteine. (barrowneuro.org)
Similar results were obtained using AAV-mediated α-synuclein overexpression as an alternative means of driving α-synuclein aggregation in vivo. (barrowneuro.org)
c-Abl activation in turn promotes α-synuclein aggregation, in a feed-forward interaction. (barrowneuro.org)
Synucleinopathies are a category of neurodegenerative diseases defined by the abnormal aggregation and accumulation of misfolded alpha-synuclein protein molecules within the brain. (nih.gov)

Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally in Parkinson's disease, Lewy body disease, and other neurodegenerative diseases. (wikipedia.org)
Alpha-synuclein is a protein that can clump to form Lewy bodies and lewy neurites, which are a hallmark of Parkinson's disease. (michaeljfox.org)
A key therapeutic target in PD is α-synuclein (αS), which is both genetically implicated and accumulates in Lewy bodies rich in vesicles and other lipid membranes. (nih.gov)
Parkinson's disease is characterized by neuronal death in the substantia nigra and the presence of intracellular inclusions of α-synuclein in the Lewy bodies. (unboundmedicine.com)
alpha-Synuclein (alpha-syn) is a small protein known to be linked to PD etiology, and though a clear biological role has not been established, aggregated forms of alpha-syn in cellular inclusions known as Lewy bodies are a diagnostic hallmark of the disease. (nih.gov)
In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. (jci.org)
Parkinson's disease is also characterized by abnormal presence of soluble toxic forms of α-synuclein that, when clustered into Lewy bodies, represents one of the pathological hallmarks of the disease. (unimi.it)
The 140-amino-acid protein α-synuclein (α-syn) is the major constituent of Lewy bodies. (nih.gov)
Due to these pathophysiologicalcharacteristics, PD clinical motor symptoms range from muscular rigidity to akinesia,resting tremor, postural instability and lately, in several nonmotor symptoms.Intracellular inclusions of aggregated α-synuclein (α-Syn) in the form of Lewy Bodies(LBs) are the main hallmark of this disease. (uc.pt)
Mutations in and alterations in expression levels of alpha-synuclein cause autosomal dominant early onset heredity forms of Parkinson's disease, and sporadic Parkinson's disease is defined in part by the presence of Lewy bodies and Lewy neurites that are composed primarily of alpha-synuclein deposited in an aggregated amyloid fibril state. (en-journal.org)
1. Ohtake, H. et.al: Beta-synuclein gene alterations in dementia with Lewy bodies. (signalchem.com)
A contribution of α-Synuclein (α-Syn) to etiology of Parkinson´s disease (PD) and Dementia with Lewy bodies (DLB) is currently undisputed, while the impact of the closely related β-Synuclein (β-Syn) on these disorders remains enigmatic. (mbexc.de)
Deposition of the pathological α-synuclein (αSynP) in the brain is the hallmark of synucleinopathies, including Parkinson disease (PD), Lewy body dementia (LBD), and multiple system atrophy (MSA). (nih.gov)
The presynaptic α-synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson's disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. (elsevierpure.com)
The neuronal cell death appeared to be correlated with the Rab5A-specific endocytosis of α-synuclein that subsequently caused the formation of Lewy body-like intracytoplasmic inclusions. (elsevierpure.com)
A hallmark of Parkinson's disease is the presence of Lewy bodies-abnormal clumps of protein primarily made of alpha-synuclein-the reduction of which is hypothesized to stop or slow the development and progression of Parkinson's and related diseases such as dementia with Lewy bodies and multiple system atrophy. (cndlifesciences.com)
We propose that the fibril morphology of serum α-synuclein seeds and aggregates derived by IP/RT-QuIC can discriminate between Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). (vbiognostics.com)
A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. (medlineplus.gov)
Beyer K, Domingo-Sabat M, Santos C, Tolosa E, Ferrer I, Ariza A. The decrease of beta-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies. (medlineplus.gov)
Beta-synuclein gene alterations in dementia with Lewy bodies. (medlineplus.gov)
For example, in its current embodiment, this assay has been used to detect alpha-synuclein seeds in cerebral spinal fluid from living patients with Parkinson's disease and Lewy-body dementia, giving high diagnostic sensitivity and specificity with unprecedented speed. (nih.gov)
A characteristic feature of this condition is Lewy bodies, which are abnormal clusters of alpha-synuclein protein in the brain. (nih.gov)
In dementia with Lewy bodies, SNCA gene mutations lead to the production of an alpha-synuclein protein with an abnormal shape. (nih.gov)
Many brain cells of people with Parkinson's contain Lewy bodies, which are unusual clumps of the protein alpha-synuclein. (nih.gov)

Alpha-synuclein (α-Syn) plays a pivotal role as the conversion of its soluble form into insoluble α-Syn aggregates represents a key event in the pathogenesis of Parkinson's disease (PD) [1] , [2] . (plos.org)
PFF injection at dentate gyrus (DG) templates the formation of endogenous α-synuclein aggregates in axons and cell bodies of this region that spread to CA3 and CA1 regions. (biomedcentral.com)
Slices derived from genetically engineered mice or manipulated using viral vectors allow testing of hypotheses on mechanisms involved in the formation of α-synuclein aggregates and their prion-like spreading. (biomedcentral.com)
The presynaptic protein α-Synuclein (α-Syn) abnormally aggregates in the brains of Parkinson's Disease patients. (tdl.org)
Now, researchers from Juntendo University (Tokyo, Japan) and Nagasaki University (Japan) have developed a novel assay that can not only reliably detect α-synuclein aggregates, but also differentiate between neurodegenerative diseases based on the type of α-synuclein aggregates present. (vbiognostics.com)
Targeting neurotoxic alpha-synuclein aggregates for Parkinson's disease therapy. (sbir.gov)
Parkinson's disease (PD) and related neurodegenerative disorders, termed the synucleinopathies, are characterized pathologically by the accumulation of protein aggregates containing α-synuclein (aSyn), resulting in progressive neuronal loss. (nih.gov)
α-synuclein aggregates induce c-Abl activation and dopaminergic neuron" by Soumitra Ghosh, Seok Joon Won et al. (barrowneuro.org)
These findings show that α-synuclein aggregates induce c-Abl activation by a redox stress mechanism. (barrowneuro.org)

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)
Given that the CSPα knockout mice had trouble assembling SNARE complexes, the researchers figured α-synuclein might compensate for its absence by helping SNARE proteins work properly. (alzforum.org)
Furthermore, α-synuclein antibodies immunoprecipitated SNARE proteins from mouse brains or cell lines that co-expressed the proteins. (alzforum.org)
However, when individual SNARE proteins were co-expressed with α-synuclein, only synaptobrevin-2 came down with the anti-synuclein antibody. (alzforum.org)
peroxidation product that can structurally alter proteins and induce α- synuclein oligomers. (edwardbetts.com)
overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins. (edwardbetts.com)
NIA recently awarded the research team a grant (U19AG062418) to further explore the spread of alpha-synuclein proteins and how this process can lead to specific neurodegenerative disease, including Alzheimer's disease and Parkinson's disease. (nih.gov)
2005) reveal that alpha-synuclein acts as a molecular chaperone, assisting in the folding and refolding of synaptic proteins called SNAREs. (nih.gov)
The addition of high concentrations of different polymers (proteins, polysaccharides and polyethylene glycols) dramatically accelerated α-synuclein fibrillation in vitro. (usf.edu)
Beta-synuclein is a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. (signalchem.com)
To begin to understand these differences, Dr. Lee is currently investigating the mechanisms of amyloid formation for two human proteins: α-synuclein, which is localized to nerve terminals and associated with Parkinson's disease, and Pmel17, which serves as structural scaffolding for melanin deposition in skin and eyes. (nih.gov)
These seeds attract other α-synuclein proteins, which results in larger clumps. (vbiognostics.com)
IP/RT-QuIC works by isolating α-synuclein seeds from a patient's serum sample via immunoprecipitation, a process where an antibody binds to a target protein and separates it from other proteins in the serum. (vbiognostics.com)

Those areas were linked to higher expression of SNCA , the gene that encodes alpha-synuclein, leading the researchers to incorporate SNCA expression into their computer model. (nih.gov)
Molecular cloning of the SNCA gene encoding alpha-synuclein from Greenland shark. (au.dk)
A ) Relative quantitation of Gapdh , α-synuclein ( Snca ), cholecystokinin ( Cck ), and peptide YY ( Pyy ) mRNAs in STC-1 and SH-SY5Y cells showing that α-synuclein mRNA is present in STC-1 cells. (jci.org)
B ) Coomassie Blue-stained 4%-12% gradient SDS-PAGE gel and corresponding immunoblot of STC-1 cells, A53T mouse brain, and Snca -/- mouse brain extracts with α-synuclein monoclonal antibody. (jci.org)
Alpha-Synuclein (SNCA) is a member of the Synuclein family. (abeomics.com)
Objective: Preclinical studies implicate the gene encoding the alpha synuclein protein (SNCA) in the pathophysiology of alcohol dependence and dopamine neuron function. (psu.edu)
The SNCA gene provides instructions for making a small protein called alpha-synuclein. (nih.gov)

After a great discussion of previous alpha-synuclein fibril structures, Manuel Schweighauser of the LMB will talk about his recent cryo-EM structures of α-synuclein reconstructed from MSA patients. (cam.ac.uk)
Watson, M.D. & Lee, J.C. (2019) N-terminal acetylation affects α -synuclein fibril polymorphism, Biochemistry , 58, 3630-3633. (nih.gov)
synuclein fibril. (bvsalud.org)
Sortilin acts as an endocytic receptor for α-synuclein fibril. (bvsalud.org)

It is well established that the abundant neuronal protein alpha-synuclein has a causal role in Parkinson's disease, yet the normal functions of this protein remain unclear. (nih.gov)

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)
Alpha-synuclein (α-Syn) plays a pivotal role in the pathophysiology of Parkinson's disease (PD), which can partly be modulated by innate and adaptive immune functions, and vice versa. (plos.org)
The aim of this study was to determine whether there is a relationship between alpha-synuclein (α-syn), a key protein in Parkinson's disease pathogenesis, and abnormalities in glucocerebroside (GC) catabolism that lead to the development of Gaucher disease. (sri.com)
Hence, we used a Parkinson's disease animal model based on unilateral injection of a recombinant adeno-associated viral vector encoding α-synuclein in the rat midbrain. (unboundmedicine.com)
Our data suggest that chronic administration of intranasal deferoxamine may be a valid approach to limiting the mishandling of α-synuclein in the central nervous system observed in Parkinson's disease and slowing disease progression. (unboundmedicine.com)
Left, yeast sick with too much α-synuclein, a protein that is implicated in Parkinson's disease. (nih.gov)
However, α-synuclein oligomers might also directly affect synaptic transmission and plasticity in Parkinson's disease models. (unimi.it)
We also found that treatment of striatal slices with antibodies targeting α-synuclein prevents the α-synuclein-induced loss of long-term potentiation and the reduced synaptic localization of GluN2A NMDA receptor subunit suggesting that this strategy might counteract synaptic dysfunction occurring in Parkinson's disease. (unimi.it)
Alpha-synuclein is a small neuronal protein that is closely associated with the etiology of Parkinson's disease. (en-journal.org)
2. Lavedan, C. et.al: Absence of mutation in the beta- and gamma-synuclein genes in familial autosomal dominant Parkinson's disease. (signalchem.com)
The intrinsically disordered protein α-synuclein (αS), a known pathogenic factor for Parkinson's disease, can adopt defined secondary structures when interacting with membranes or during fibrillation. (uni-konstanz.de)
The results of the study suggest that the TLR2/MyD88/NF-κB pathway is important in the spread of alpha-synuclein and that wtTIDM and wtNBD may be useful in the treatment of Parkinson's disease and other synucleinopathies. (cndlifesciences.com)
Synucleiopathies are neurodegenerative diseases, such as Parkinson's disease (PD), that are characterized by the accumulation of incorrectly folded α-synuclein, a protein abundant in the brain. (vbiognostics.com)
Moreover, the incubation of cells with ammonium chloride or bafilomycin A1 to produce the lysosomal dysfunction recently reported in Parkinson's disease led to an increase in the release of alpha-synuclein in exosomes and a concomitant increase in alpha-synuclein transmission to recipient cells. (ox.ac.uk)
Cell -to- cell spreading of misfolded α- synuclein (αSYN) is supposed to play a key role in the pathological progression of Parkinson's disease (PD) and other synucleinopathies . (bvsalud.org)
Head injury, alpha-synuclein Rep1, and Parkinson's disease. (cdc.gov)

They pulled out the complexes using antibodies to the SNARE protein SNAP-25, and found α-synuclein in the mix. (alzforum.org)

Moreover, in last week's PNAS Early Edition, Mark Gluck, Rutgers University, Newark, New Jersey, and colleagues report finding impaired learning in people who have two copies of the α-synuclein gene and are predisposed to Parkinson's but lack, as yet, PD-like symptoms. (alzforum.org)
glial cell line-derived neurotrophic factor), the regulation of the α- synuclein and Parkin gene expression. (edwardbetts.com)
The final result-a brain network model that visualizes alpha-synuclein spreading based on brain connectivity and gene expression-provides a new method to "test different hypotheses of spreading patterns, timing, directionality and vulnerability," according to an accompanying editorial. (nih.gov)
More recently, she has studied the interaction between α-synuclein and glucocerebrosidase, the enzyme deficient in Gaucher disease, to explain why mutations in GBA, the gene encoding glucocerebrosidase, is a risk factor for Parkinsonism. (nih.gov)
By stimulating the cells of mice to form alpha-synuclein, researchers observed an increased interaction between toll-like receptor 2 (TLR2) and the MyD88 gene, which increases the activity of a third player, nuclear factor kappa B (NF-κB). (cndlifesciences.com)
The SNCB gene provides instructions for making a protein called beta-synuclein. (medlineplus.gov)

However, certain areas of alpha-synuclein accumulation occurred outside those pathways. (nih.gov)
We found that inhibition of OGA by thiamet G at nanomolar concentrations significantly increased protein O-GlcNAcylation, activated MTOR, decreased autophagic flux, and increased α-synuclein accumulation, while sparing proteasomal activities. (biomedcentral.com)
Inhibition of MTOR by rapamycin decreased basal levels of protein O-GlcNAcylation, decreased AKT activation and partially reversed the effect of thiamet G on α-synuclein monomer accumulation. (biomedcentral.com)
Pathologic accumulation of α-synuclein is a feature of human parkinsonism and other neurodegenerative diseases. (elsevierpure.com)
It is thought that this altered protein may not be able to prevent alpha-synuclein accumulation. (medlineplus.gov)

Described in a study funded in part by NIA and published in Nature Neuroscience , the model is the first to incorporate both brain connectivity and genetic risk factors involved in abnormal alpha-synuclein spread. (nih.gov)
It is conceivable that these neuronal mechanisms of protein clearance play an important role in neurodegenerative processes characterized by abnormal α-synuclein buildup. (elsevierpure.com)
CND Life Sciences is the creator of the Syn-One Test™, the world's first commercially available test to visualize abnormal, phosphorylated alpha-synuclein in cutaneous nerve fibers. (cndlifesciences.com)

This technology enables rapid, economical and ultrasensitive detection of disease-associated forms of alpha-synuclein as biomarkers or indicators of synucleinopathy in a biological sample. (nih.gov)
We were surprised that pathogenic forms of alpha-synuclein were so pervasive in the appendixes of people both with and without Parkinson's. (nih.gov)

Spread of alpha-synuclein pathology from a single injection site (dark orange) on the right hemisphere of a mouse brain and a network model of that spread on the left. (nih.gov)
To understand the spread of alpha-synuclein in more detail, the researchers created a computer-based "network diffusion" model using a map of mouse brain regions and connecting pathways. (nih.gov)
The mechanisms behind the formation of spread of alpha-synuclein are not well understood, but a paper published last month in Nature Communications sheds light on a signaling pathway that may prove to be a therapeutic target in these neurodegenerative diseases. (cndlifesciences.com)

The normal function of alpha-synuclein is poorly understood, and the precise mechanisms by which it leads to toxicity and cell death are also unclear. (en-journal.org)
Although the function of alpha-synuclein is not well understood, studies suggest that it plays an important role in maintaining an adequate supply of synaptic vesicles in presynaptic terminals. (nih.gov)
Researchers are working to determine whether these changes alter the function of alpha-synuclein and how they influence the risk of developing multiple system atrophy. (nih.gov)

Enzyme immunoassay for the quantitative determination of beta-sheet oligomers of human alpha-Synuclein in biological samples. (roboscreen.com)
The Human alpha-Synuclein PATHO ELISA bases on a sensitive sandwich ELISA using mab 5G4 for capturing of beta-sheet oligomers of human alpha-Synuclein (Kovacs et al. (roboscreen.com)

A strong band at about 17 kDa corresponds to beta-synuclein protein. (biosensis.com)

We created a two-hit [neuroinflammation and mutant α-synuclein (α-syn) overexpression] animal model to investigate mechanisms through which mutant α-syn and inflammation work in concert to mediate chronic PD neurodegeneration. (nih.gov)
When neuronal α-synuclein expression was enhanced as a result of toxic injury (i.e. treatment of mice with the herbicide paraquat) or transgenic protein overexpression, the intralysosomal content of α-synuclein was also significantly increased. (elsevierpure.com)

Analysis of intracellular parameters of cellular energy metabolism revealed that the co-expression of mutant alpha-synucleins in HEK-hDAT cells accelerates the reduction of intracellular net ATP levels and ATP/ADP ratios induced by 6-OHDA. (unboundmedicine.com)

Taken together, our data show that in vivo iron chelation can modulate α-synuclein-induced pathology in the central nervous system. (unboundmedicine.com)
This suggests a model in which PD pathology originates in the gut and spreads to the central nervous system via cell-to-cell prion-like propagation, such that transfer of misfolded α-synuclein initiates misfolding of native α-synuclein in recipient cells. (jci.org)
This study clearly demonstrates the importance of exosomes in both the release of alpha synuclein and its transmission between cells and suggests that factors associated with PD pathology accelerate this process. (ox.ac.uk)

Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. (nih.gov)
α-Synuclein A30P decreases neurodegeneration and increases synaptic vesicle release probability in CSPα-null mice. (nih.gov)

Alpha synuclein in neurodegenerative disorders: murderer or accomplice? (wikipedia.org)

Beta-synuclein is shown to be highly expressed in the substantia nigra of the brain, a region of neuronal degeneration in patients with Parkinson disease but no direct relation to Parkinson disease has been established (1). (signalchem.com)

alpha-Synuclein beta-sheet oligomers captured onto the plate are detected by another alpha-Synuclein specific mab to amino acids 119-126 HRP conjugated. (roboscreen.com)

Our data show that although intranasal administration of deferoxamine in rats did not protect them from dopaminergic cell death, it did decrease the number of the pathological α-synuclein formations at the terminal level. (unboundmedicine.com)
Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded α-synuclein is found in enteric nerves before it appears in the brain. (jci.org)
Here we review the known features of alpha-synuclein membrane interactions in the context of both the putative functions of the protein and of its pathological roles in disease. (en-journal.org)

Here we examined the pathogenic mechanism of neuronal cell death induced by α-synuclein. (elsevierpure.com)

The gamma-synuclein protein's expression in breast tumors is a marker for tumor progression. (wikipedia.org)

Mutant (A30P and A53T) alpha-synuclein isoforms cause increased vulnerability of cells towards various toxic insults and enhance dopamine transporter (DAT)-mediated toxicity of the selective dopaminergic neurotoxin and mitochondrial complex I inhibitor MPP(+) in vitro. (unboundmedicine.com)
We studied the cytotoxicity as well as the toxic mechanisms of 6-OHDA in human embryonic kidney HEK-293 cells ectopically co-expressing mutant alpha-synucleins and the human DAT protein. (unboundmedicine.com)
6-OHDA showed half-maximal toxic concentration (TC(50)) of 88 microM in HEK-hDAT cells without alpha-synuclein expression after 24 h, whereas the TC(50) values significantly decreased to 58 and 39 microM by expression of A30P and A53T alpha-synuclein, respectively. (unboundmedicine.com)
Right, the same yeast cells after a dose of NAB, which seems to reverse the toxic effects of α-synuclein. (nih.gov)
The team also found a build-up of the toxic form of alpha-synuclein in the appendixes of healthy volunteers. (nih.gov)

Mouse anti-Beta-synuclein Monoclonal Antibody (Unconjugated), suitable for WB, IHC-Frozen. (biosensis.com)

α-synuclein "does not act acutely in synaptic transmission," said lead investigator Thomas Südhof, Stanford University, Palo Alto, California, in an interview with ARF. (alzforum.org)
This puzzled the scientists because transgenic α-synuclein does not seem to affect synaptic strength. (alzforum.org)
The beta-synuclein antibody detects protein concentrated in synaptic regions, while the NF-L antibody labels dendrites and axons of neuronal cells. (biosensis.com)

Immunogen Description C-terminal peptide of human β-synuclein (EPEGESYEDPPQEEYQEYEPEA) coupled to KLH. (biosensis.com)

Beta-synuclein may play a role in neuronal plasticity, is abundant in neurofibrillary lesions of patients with Alzheimer disease. (signalchem.com)
Alpha-synuclein is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. (nih.gov)

Furthermore, iron can compromise the solubility of α-synuclein through direct interaction and can induce neurotoxicity in vitro. (unboundmedicine.com)
Our data suggest a mechanism of 6-OHDA-induced dopaminergic toxicity involving an interaction of mutant alpha-synucleins with the DAT molecule and subsequent acceleration of cellular energy depletion that might be relevant for the pathogenesis of PD. (unboundmedicine.com)

Furthermore, it allowed development of slices expressing only serine-129 phosphorylation-deficient human α-synuclein (S129G) using an adeno-associated viral (AAV) vector in α-synuclein knockout slices. (biomedcentral.com)

The data hint that α-synuclein mutations could have subtle effects that result from neurotransmission problems. (alzforum.org)

Although alpha-synuclein is a highly soluble, cytoplasmic protein, it binds to a variety of cellular membranes of different properties and compositions. (en-journal.org)

Sebastian Hiller와 그의 동료들은 시험관 내(In vitro) 및 세포에서 핵 자기공명을 이용하여 번역 후 수정 의존적으로 α-synuclein에 결합하여 생체 내 α-synuclein의 축적을 억제하는 6개의 샤페론을 발견하였다. (natureasia.com)
Intrastriatal injections of α-synuclein produce deficits in visuospatial learning associated with reduced function of GluN2A NMDA receptor subunit indicating that this protein selectively targets this subunit both in vitro and ex vivo. (unimi.it)

α-Synuclein (α-syn) is closely associated with both familial and sporadic PD. (nih.gov)

It is known to reverse toxicity of mutant α- synuclein , TDP-43, FUS, and TAF15 in yeast cells. (edwardbetts.com)
alpha-Synuclein expression did not affect 6-OHDA toxicity in HEK-293 cells not expressing the DAT. (unboundmedicine.com)

Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. (ox.ac.uk)

Furthermore, quantifying the distribution of alpha-synuclein in vivo could improve our understanding of disease progression. (michaeljfox.org)
In this study, lysosomal clearance of α-synuclein in vivo was indicated by the detection of α-synuclein in the lumen of lysosomes isolated from the mouse midbrain. (elsevierpure.com)
The data provide in vivo evidence of lysosomal degradation of α-synuclein under normal conditions and, quite importantly, under conditions of enhanced protein burden. (elsevierpure.com)

A tracer for imaging alpha-synuclein mRNA could improve early diagnostic accuracy for Parkinson's. (michaeljfox.org)

Methodology/Principal Findings: Here, we show that α-synuclein adopts a variety of conformations in primary neuronal cultures using fluorescence lifetime imaging microscopy (FLIM). (elsevierpure.com)

Dopamine also induced conformational changes in α-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species. (elsevierpure.com)
These alterations cause the alpha-synuclein protein to take on an incorrect 3-dimensional shape (misfold). (nih.gov)

Anatomy3

Organisms1

Diseases3

Chemicals and Drugs7

Psychiatry and Psychology1

Phenomena and Processes1

Information Science2

Fibrils6

Neurons16

Aggregation15

Lewy24

Aggregates9

Proteins16

SNCA7

Fibril4

Protein alpha-synuclein1

Parkinson's Disease16

Antibodies1

Gene6

Accumulation5

Abnormal3

Forms of alpha-synuclein2

Spread of alpha-synuclein3

Function of alpha-synuclein3

Human Alpha-Synuclein2

Beta-synuclein protein1

Overexpression2

Intracellular1

Pathology3

Neurodegeneration2

Neurodegenerative disorders1

Substantia nigra1

Oligomers1

Pathological3

Pathogenic1

Gamma-synuclein1

Toxic5

Monoclonal1

Synaptic3

Peptide1

Abundant2

Interaction2

Adeno-associated viral1

Mutations1

Soluble1

Vitro2

Familial1

Toxicity2

Dysfunction1

Vivo3

MRNA1

Neuronal cultures1

Alterations2