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Validated All-in-One™ qPCR Primer for SNCA(NM_001146055.2) Search again
Product ID:
HQP161120
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
NACP, PARK1, PARK4, PD1
Gene Description:
synuclein alpha
Target Gene Accession:
NM_001146055.2(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Summary
Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Four alternatively spliced transcripts encoding two different isoforms have been identified for this gene. [provided by RefSeq].
Gene References into function
- Protofibrillar alpha-synuclein, in contrast to the monomeric and fibrillar forms, binds synthetic vesicles very tightly via a beta-sheet-rich structure, causing transient and potentially cytotoxic permeabilization.
- alpha-synuclein expression in human neurons is up-regulated during differentiation
- Alpha-synuclein protofibril is stabilized by a dopamine-alpha-synuclein adduct.
- we investigated the effects of inhibitors of the mitochondrial electron-transport chain on the aggregation of alpha-synuclein, a major protein component of Lewy bodies
- Variations in a complex repeat (NACP-Rep1) c. 10 kb upstream are associated with various levels of expression of the gene.
- familial Parkinson's disease-linked A30P mutant alpha-Syn is defective in binding to phospholipid vesicles in vitro as determined by vesicle ultracentrifugation, circular dichroism spectroscopy, and low-angle X-ray diffraction
- Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins
- Results show that Ser-129 of alpha-synuclein is selectively and extensively phosphorylated in synucleinopathy lesions, and that this phosphorylation promoted fibril formation in vitro.
- The extent of formation of amyloid fibrils from alpha-synuclein is greatly enhanced by heparin and certain other glycosaminoglycans and charged polymers in vitro, observations that are relevant in the context of the etiology of Parkinson's disease.
- overexpression of human alpha-synuclein, particularly the mutant form, can cause human DA neuron death, suggesting that alpha-synuclein may have a primary role in the pathogenesis of PD.
- alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells
- directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila model of Parkinson's disease
- These findings provide a link between mutations or over-expression of alpha-synuclein and apoptosis of dopaminergic neurons by lowering the threshold of these cells to oxidative damage.
- its structural change including the post translational protein processing is a future interest in the molecular mechanism of multiple system atrophy
- observation that amino acid residues 31-109 of constitute the core unit of the filaments
- acceleration of fibrillization by molecular crowding
- mutated in parkinson disease, also a major component of Lewy bodies
- neurotoxicity is a mechanism for selective neurodegeneration in Parkinson disease.
- Data show that both normal and mutant alpha-synuclein specifically interact with the mitochondrial complex IV enzyme, cytochrome C oxidase.
- The fibrillation of alpha-synuclein at neutral pH was completely inhibited by methionine oxidation.
- Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred.
- Ala-53-->Thr mutation causes neurodegenerative disease in transgenic mice
- the NAC sequence is essential to beta-sheet formation and the aggregation originates from the beta-sheet intermediate, which may be implicated in the pathogenesis of Parkinson's disease
- overexpression of wild-type or mutated human alpha-synuclein leads to dopamine neuronal cell death in rodents
- mutant proteins form annular protofibrils(similar to pore-forming bacterial toxins), suggesting that inappropriate membrane permeabilization might be the cause of cell dysfunction and even cell death in amyloid diseases, as Alzheimers and Parkinsons
- role in pathogenesis of Parkinson disease
- These results suggest that mutant alpha-synuclein leads to an impairment in vesicular dopamine storage and consequent accumulation of dopamine in the cytosol.
- new mechanism of MPP+-induced dopaminergic toxicity by an interaction between mutant alpha-synucleins and the DAT, which is independent of the function of the proteasome.
- effects of pH and salt concentration on the in vitro assembly of human wild-type alpha-synuclein, particularly with regard to aggregation rate and aggregate morphology
- functions as a negative regulator of Ca(++)-dependent alpha-granule release from human platelets
- characterized the cytoplasmic alpha-synuclein aggregates using a fractionation procedure with which different aggregate species can be separated
- Two mutations in the alpha-synuclein gene (A30P and A53T) promote the formation of alpha-synuclein protofibrils, suggesting a causal role for protofibril formation in Parkinson disease.
- examined the biochemical characteristics of the additional, higher molecular mass species of phosphorylated alpha-synuclein-positive polypeptides that also are recovered in the Sarkosyl-insoluble fraction of synucleinopathy
- role of alpha-synuclein in the pathobiology of Parkinson's disease (review)
- conformational behavior of human alpha-synuclein is modulated by familial Parkinson's disease point mutations A30P and A53T
- Polymorphism of the alpha synuclein promoter region (non-amyloid component of plaques (NACP)-Rep1) is associated with an increased risk of Parkinson's disease (PD) in three separate studies.
- The number of the N-terminal repeat domain in wild-type alpha-synuclein represents an evolutionary balance between the functional conformer of alpha-synuclein (alpha-helix and/or random coil) and its pathogenic beta-sheet conformation.
- The critical rate-limiting step in nucleation of alpha-synuclein fibrils under physiological conditions is the oxidative formation and accumulation of a dimeric, dityrosine cross-linked prenucleus.
- proteasomal inhibition by aggregated alpha-synuclein could be mediated by interaction with S6'.
- role of aggregation by tissue transglutaminase in Lewy body formation in Parkinson's disease and dementia with Lewy bodies
- conformation assumed upon binding to phospholipid membranes consists of two alpha-helical regions interrupted by a short break, which may be important for its pathogenic role
- Mutant alpha-synuclein accumulation impairs short-term changes in synaptic strength when neurotransmitter availability is limited due to enhanced release probability or repetitive synaptic activity.
- A normal function of alpha-synuclein is the negative modulation of human dopamine transporter (hDAT) activity.
- While over-expression of the mutant forms of alpha-synuclein enhances cell death in cells exposed to ischemia/reoxygenation or staurosporine, the wild type of alpha-synuclein protects against serum withdrawal-induced death and dopamine-induced toxicity.
- Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons.
- results suggest that interactions between alpha-synuclein and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases
- In neural cells transfected with either normal or mutant A30P or A53T alpha-synuclein, downregulation of GTP cyclohydrolase, sepiapterin reductase, tyrosine hydroxylase and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein was noted
- Mice overexpressing alpha-synuclein, either the human wild-type or the Ala53Thr mutant form of the protein, displayed paraquat-induced protein aggregates but were completely protected against neurodegeneration
- The results show an absence of protective effects for the A30P/A53T mutants, and a differential cytoprotective role of alpha-synuclein against oxidants, which varies according to expression levels.
- The alpha-synPD patients presented the illness at a younger age and also had lower prevalence of tremor when compared with the fPD patients.
- Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-synuclein or both; no immunoreactivity for gamma-synuclein is seen in medulloblastomas.
- The identification of pathogenic mutations in the three genes alpha-synuclein, parkin, and UCHL1 has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD).
- Caenorhabditis elegans transgenic for human alpha-synuclein demonstrate neuronal and behavioral perturbations that are dependent upon expression in specific neuron subtypes
- Alpha-synuclein, but not its mutants (A53T, A30P), can protect CNS dopaminergic cells from the parkinsonism-inducing drug MPP+ but not from other neurotoxic agents tested
- alpha-synuclein has a highly dynamic structure, in agreement with the notion that alpha-synuclein is a natively unfolded protein. In contrast, fibrillar aggregates of alpha-synuclein exhibit a distinct domain organization.
- Our results did not confirm the association reported previously and failed to identify a alpha-synuclein specific haplotype as susceptibility factor for essential tremor.
- These results suggest that ubiquitination of alpha-synuclein is not required for inclusion formation and follows the fibrillization of alpha-synuclein.
- nitrative and/or oxidative stress results in distinct mechanisms of alpha-synuclein protein modifications that can influence the formation of stable alpha-synuclein fibrils
- translocation into the nucleus and binding with histones represent potential mechanisms underlying alpha-synuclein pathophysiology
- The carboxy-terminus of alpha-syn may regulate aggregation of full-length alpha-syn and determine the diameter of alpha-syn filaments
- Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein
- alpha-synuclein overexpression augmented TNF-alpha-induced apoptotic cell death in U373 cells by induction of caspase activation
- oxidative stress, stress-activated kinases, and factors involved in autophagy up-regulate alpha-synuclein content.
- The ability of alpha-synuclein to disrupt membranes correlated with the binding affinity of alpha-synuclein for the particular membrane lipid composition, and to the induced helical conformation of alpha-synuclein.
- Hyperosmotic stress induced phosphorylation of tyrosine 125 of alpha-synuclein via Pyk2/RAFTK; such phosphorylation was inhibited by related adhesion focal tyrosine kinase-associated protein
- consecutive cycles of compression-decompression under aggregating conditions lead to reversible dissociation of transthyretin and alpha-synuclein fibrils
- data suggest that accumulation of modified 22-24-kDa alpha-synuclein is a disease-specific event which may overwhelm the proteolytic system, leading to aberrant ubiquitination
- an analysis of the intra-allelic variation at NACP-Rep1 in the alpha-synuclein gene
- alpha-synuclein degradation and the pathogenesis of synucleinopathies are regulated by neurosin
- alpha-synuclein plays a role in neurotransmitter release and synaptic plasticity--REVIEW
- anionic surfaces presented as micelles or vesicles can serve to nucleate alpha-synuclein fibrillization
- alphaS-PUFA interactions help regulate neuronal PUFA levels as well as the oligomerization state of alphaS, both normally and in human synucleinopathies
- Behavior analysis of transgenic mice expressing A53T mutant human alpha-synuclein shows a progressive reduction of spontaneous vertical motor activity in both mutant lines correlating with the dosage of overexpression.
- In the present study we genotyped the NACP-REP1 polymorphism in 189 PD patients from southern Italy and 182 healthy control subjects. We failed to demonstrate an association of any NACP-REP1 allele with PD.
- Quantitative real-time PCR amplification of SNCA exons yielded results consistent with whole gene triplication in a Parkinson disease family
- Membrane-bound alpha-synuclein associates at the interfacial region of the lipid bilayer where it may favor a local concentration of certain phospholipids.
- role of aggresomes in cell viability was addressed in the context of over-expressing alpha-synuclein and its interacting partner synphilin-1
- Casein kinase II (CKII) phosphorylates synphilin-1; beta subunit of this enzyme complex binds to synphilin-1. CKII-mediated phosphorylation of synphilin-1, rather than alpha-synuclein, modulates the aggregation into inclusion bodies.
- genome-wide screens were performed in yeast to identify genes that enhance the toxicity of alpha-synuclein; genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport
- when expressed in yeast, it associated with the plasma membrane in a highly selective manner, before forming cytoplasmic inclusions; inhibited phospholipase D, induced lipid droplet accumulation, and affected vesicle trafficking
- Peripheral nerve studies show that alpha-synuclein (alpha-Syn) is almost exclusively transported in the slow component of axonal transport and that familial Parkinson's disease-linked alpha-Syn mutations have no obvious effects on its axonal transport.
- Pathological alpha-synuclein associated with inclusions in Parkinson disease is first evident as punctate perikaryal material that, via incorporation of p62 and ubiquitin, yields pale body-type structures from which Lewy body-type inclusions form.
- cysteine substitution at critical positions in the alpha-synuclein molecule can increase dimer formation and accelerate protein aggregation and cellular toxicity of alpha-synuclein
- alpha-synuclein filaments and oligomers have roles in proteasome inhibition
- Alpha-synuclein is up-regulated during apoptosis in neuroblastoma cells
- Review highlights the debate about the precise mechanisms of alpha-synuclein toxicity to vulnerable neurons in the pathogenesis of Parkinson's disease.
- the reduced axonal transport exhibited by Parkinson's disease-associated alpha-synuclein mutants might contribute to perikaryal accumulation of alpha-synuclein and hence Lewy body formation and neuritic abnormalities in diseased brain
- Alpha-Synuclein expression was observed in all fetal human organs examined. In adult human tissues the high expression of alpha-synuclein was maintained in the brain, whereas in other organs the expression was greatly reduced.
- Alpha-synuclein has a high affinity for packing defects in a bilayer membrane
- Loss of alpha-synuclein may contribute to frontal lobe dysfunction in aging and Alzheimer's disease, and may reflect subtle loss of presynaptic proteins in intact synapses.
- Methionine oxidation plays an important role in inhibiting alpha-synuclein aggregation; the degree of inhibition of fibrillation by alpha-synuclein is proportional to the number of oxidized methionines.
- Neither the Ala53Thr nor the Ala30Pro mutation has a significant effect on the structure of folded alpha-synuclein. The Ala30Pro, but not the Ala53Thr, mutation appears to decrease the affinity of the protein for lipid surfaces.
- Results suggest that the C-terminal domain acts as a regulator of alpha-synuclein aggregation.
- Authors' review shows that alpha-synuclein expression in the peripheral immune system might be one of the primary causes of immune abnormalities in patients with Parkinson's disease.
- Ubiquitin, HSP27, parkin, and alpha-synuclein are cross-linked by gamma-glutamyl-epsilon-lysine bonds in Alzheimer's neurofibrillary tangles. Gln(99) is the site of the bond in synuclein.
- alpha-synuclein has a vital role in the modulation of dopamine transporter (DAT) function (review)
- Results describe the structure of membrane-bound alpha-synuclein.
- SNCA triplication causes doubling of plasma alpha-synuclein & of its mRNA level in brain. At the protein level in brain, there is a greater effect on aggregated form deposition into insoluble fractions than on soluble alpha-synuclein expression.
- Amino acid residues 64-100 of alpha-syn are the binding region responsible for its self-association.
- In cases of Lewy body disease (LBD), alpha-synuclein does not exhibit binding to rabphilin but rather to rab3a, suggesting possible impairment of neurotransmitter exocytosis in LBD.
- consistent with the hypothesis that mutant alpha-synuclein disrupts vesicular dopamine compartmentalization, this effect was diminished in cells expressing mutant alpha-synuclein
- alpha-synuclein and alphaB-crystallin interact readily with each other and affect each other's properties, in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone action
- Review focuses on the fibrillization potential of alpha-synuclein and on its link with defects in protein degradation.
- subtle sequence changes in alpha-synuclein could significantly alter interaction with membrane bilayers
- alpha-Synuclein binds saturably and with high affinity to characteristic intracellular structures that double-label for components of lipid rafts. The A30P mutation associated with Parkinson disease disrupts this interaction.
- alpha-SN may be one of the primary causes of the immune abnormalities observed in Parkinson's disease
- The distribution of the alleles of the dinucleotide repeats variants of alpha-synuclein gene promoter region in Parkinson's disease cases was significantly different from that in the healthy controls.
- Although SNCA multiplication is a rare cause of Parkinson disease & Lewy body dementia, this study suggests other genetic variation in the SNCA gene, in trans-acting factors, & in post-transcriptional regulatory elements are likely to influence disease.
- A53T mutant human alpha-Syn exhibits increased stability in neuronal cell lines.
- wild-type alpha-synuclein is efficiently degraded in lysosomes by chaperone-mediated autophagy (CMA), but the pathogenic alpha- synuclein mutants are poorly degraded by CMA despite a high affinity for the CMA receptor
- Regulation of alpha-synuclein expression: implications for Parkinson's disease. Review.
- Data suggest that post-translational modification of alpha-syn by nitration can promote the formation of intracytoplasmic inclusions that constitute the hallmark of Parkinson disease and other synucleinopathies.
- show using human cytochrome c plus H(2)O(2) as the source oxidative stress, that the tyrosines of alpha-synuclein are required for aggregation
- data indicated that there are two distinct families of structures: one consisting of relatively compact proteins with eight or less negative charges and one consisting of relatively extended structures with nine or more charges
- Overexpression of alpha-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function.
- functional effects of missense mutation on phospholipid binding and filament assembly of alpha-synuclein
- DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation
- Data suggest that the ability of Hsp70 to prevent toxicity is distinct from degradation of alpha-synuclein and is dependent on its ATPase domain.
- total alpha-synuclein levels were just marginally elevated in dementia with Lewy bodies
- Data show that double-stranded DNA, either linear or supercoiled, interacts with wild-type alpha-synuclein, leading to a significant stimulation of alpha-synuclein assembly into mature fibrils.
- parkin-mediated neuroprotection was associated with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a key role for parkin in the genesis of Lewy bodies
- perhaps p25alpha plays a pro-aggregatory role in the common neurodegenerative disorders hall-marked by alpha-synuclein aggregates
- Real-time monitoring of stimulated dopamine release in mice with different alpha-synuclein expression was used to study the role of alpha-synuclein in presynaptic dopamine recruitment.
- the alpha- and gamma-synucleins regulate proteasomal function and beta-synuclein acts as a negative regulator of alpha-synuclein
- Abnormal alpha-synuclein aggregation in the amygdala is disease selective, but not restricted to disorders of alpha-synuclein and beta-amyloid.
- Association of synuclein into higher molecular mass oligomers/protofibrils represents an alternate pathway from filament formation.
- The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces.
- gene multiplication appears not to be a major cause in the pathogenesis of sporadic Lewy body disease and young onset Parkinson disease in European population
- Role of the membrane on the aggregation process of alpha-synuclein.
- Ubiquitination sites were found to be identical to those in filamentous alpha-synuclein. Parkinson disease-linked mutations.
- alpha-synuclein E46K mutation increases amyloid fibril formation
- Alpha-synuclein may play a role in phosphoinositol signaling that is coupled to the dopamine-G beta gamma-phospholipase C beta 2 pathway, ultimately leading to changes in calcium signaling.
- Combined analysis yielded a highly significant association between the 0 allele of the alpha-synuclein gene and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001).
- Heat shock protein 70 inhibits alpha-synuclein fibril formation
- Stabilization of the native, autoinhibitory structure of alphasynuclein constitutes a potential strategy for reducing or inhibiting oligomerization and aggregation in Parkinson's disease.
- A significantly elevated gene-specific alpha synuclein promoter DNA methylation pattern is observed in peripheral mononuclear cells of patients with chronic alcoholism.
- The association of different NACP-Rep1 alleles with Parkinson's disease may be mediated, in part, by the effect of PARP-1, on SNCA expression.
- Data demonstrate that C-terminally truncated alpha-Synuclein (alpha-SynDeltaC) is normally generated from full-length alpha-Syn independent of alpha-Syn aggregation in brains and in cultured cells.
- results provide indirect evidence on how beta-sheets assemble into alpha-synuclein fibrils on a nanometer scale
- linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1) in Parkinson disease
- Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains
- the NACP-REP1 marker within the alpha synuclein gene may be associated with alcohol dependence
- There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither. The combined effect of the two genotypes was the same as for either of the genotypes alone (separate and equal).
- Proteins associated with impaired energy metabolism and mitochondria are particularly prone to oxidative stress associated with Ala30Pro-mutant alpha-synuclein in transgenic mice.
- In a transgenic mouse model, ultrastructural analysis shows that human alpha-synuclein-enhanced green fluorescent protein overexpression results in the accumulation of electrodense inclusions and laminated bodies suggestive of lysosomal dysfunction.
- located the primary binding for Cu(II) to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry
- results suggest that nigral neuronal damage may release aggregated alpha-synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators
- decreased dopamine levels in substantia nigra neurons might promote alpha-syn aggregation in Parkinson's disease
- truncated alpha-synuclein and proteasome have roles in alpha-synuclein aggregation
- overexpression of CHIP inhibits alpha-synuclein inclusion formation and reduces alpha-synuclein protein levels
- extracellularly secreted alpha-synuclein is processed via the activation of MMP-3
- Our findings indicate that both parkin and alpha-SN share a common pathway in DA metabolism whose abnormality leads to accumulation of oxidative DA metabolites and subsequent cell death.
- The expression of the alphav integrin subunit in whole cell lysates was significantly downregulated in halpha-syn CG-4 oligodendrocyte progenitor cells. These results demonstrate a cytotoxic consequence of halpha-syn overexpression in CG-4 cells.
- Abeta enhances the development of cortical alpha-synuclein lesions in cases of Parkinson disease
- interaction between endogenous DJ-1 and alpha-synuclein in normal and diseased brain tissue
- The antiapoptotic property of Hualpha-Syn in neuronal cell lines is associated with the attenuation of caspase-3 activity without affecting the caspase-9 activity or the levels of cleaved, active caspase-3.
- A new protocol for preparing recombinant alpha-synuclein (AS) from E. coli has been developed with only two steps: (1) osmotic shock for release of AS-containing periplasm fraction and (2) ion-exchange chromatography for further purification of AS.
- Alpha-synuclein has a role in altering proteasome function, protein synthesis, and stationary phase viability
- phosphorylation of alpha-synuclein at S129 may be important for the formation of inclusions in PD and related alpha synucleinopathies
- Altered alpha-synuclein homeostasis causing Parkinson's disease.
- Intravesicular localization and secretion are part of normal life cycle of alpha-syn and might also contribute to pathological function of this protein in Parkinson disease.
- Results demonstrate that wild-type alpha-synuclein interacts with the pro-apoptotic molecules BAD and protein kinase C delta to protect dopaminergic neuronal cells against neurotoxic insults.
- We report here a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. Nucleus accumbens and limbic areas of the cerebral cortex showed vacuolation, with clustering of microvacuoles around Lewy neurites.
- Binds with higher affinity to artificial membranes with the PS head group on the polyunsaturated fatty acyl chain rather than on the oleoyl side chain, indicating a stringent combinatorial code for the interaction of alpha-synuclein with membranes.
- NMR spectroscopy demonstrates that Parkinsonism-linked mutations greatly perturb specific tertiary interactions essential for the native state of alpha-synuclein.
- agrin has a role in binding alpha-synuclein and modulating alpha-synuclein fibrillation
- Hsp70 chaperones inhibit reactive oxygen species generation and apoptosis by binding and sequestering alpha-syn
- an engineered alpha-synuclein double mutant prevents wild type and familial Parkin variant fibril formation
- Overexpression of alpha-synuclein may play a role in cocaine-induced plasticity and regulation of dopamine synaptic tone.
- structural analysis of micelle-bound human alpha-synuclein and Parkinson disease variants
- The axonal transport of tau occurs via a mechanism utilising fast transport motors, including the kinesin family of proteins, and that alpha-synuclein transport in neurons may involve both kinesin and dynein motor proteins.
- results indicate a role of microtubules in the modulation of dopamine transporter (DAT) trafficking, and provide insight into a novel mechanism by which alpha-synuclein regulates DAT activity, by tethering the transporter to the microtubular network
- DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T alpha-synuclein toxicity
- PD-related genetic modifications of human alpha-synuclein, parkin, and DJ-1 disrupt the mitochondrial function in C. elegans
- Our data provide evidence that overexpression of mutated human A30P alpha-synuclein in mice leads to a reduced size of the dopamine storage pool.
- This study showing an influence of Rep1 polymorphism on age at onset of parkinson's disease.
- Alpha-synuclein protects nerve terminals against injury and suggests that this activity operates in conjunction with CSPalpha and SNARE proteins on the presynaptic membrane interface.
- Accumulation of alpha-synuclein (alpha-syn) in oligodendrocytes of transgenic mice overexpressing human alpha-syn promotes neurodegeneration and recapitulates several of the key functional and neuropathological features of multiple system atrophy
- The Human wild type (WT) and mutant alpha-synuclein (alpha-syn) genes were overexpressed using a Tet-on expression system in stably transfected dopaminergic MN9D cells.
- A putative environmental pathogen capable of passing the gastric epithelial lining might induce alpha-synuclein misfolding and aggregation in specific cell types of the submucosal plexus and reach the brain via a consecutive series of projection neurons.
- protofibril formation of alpha-synuclein is induced by dequalinium
- identified a number of independent copper binding sites in both the lipid-binding N-terminal domain and the highly acidic C-terminal domain
- Two families with SNCA duplication were identified among autosomal dominant hereditary Parkinson's disease patients.
- Transgenic mice expressing human Ala53--> Thr Parkinson's disease mutant alpha-synuclein develop intraneuronal inclusions, mitochondrial DNA damage and degeneration, and apoptotic-like death of neocortical, brainstem, and motor neurons.
- Results suggest that DJ-1 may act as an oxidative-stress-induced chaperone to prevent alpha-synuclein fibrillation.
- 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.
- alpha-SYN aggregation in vitro was clearly accelerated by addition of FK506 binding proteins (E. coli SlyD FKBP & human FKBP12) & was counteracted by FK506, a specific inhibitor of FKBP.
- alpha-synuclein interacts with vesicle membranes containing sphingomyelin and cholesterol; the protein is capable of annealing defects in curved vesicle membranes, which may prevent synaptic vesicles from premature fusion
- SUMO1 is involved in a modification of tau and alpha-synuclein that may also have implications for their pathogenic roles in neurodegenerative diseases
- These study demonstrate abnormal and distinct alpha-synuclein solubility and aggregation, and alpha-synuclein nitration without formation of Lewy bodies in the frontal cortex in PiD.
- Our findings indicate that there is a high frequency of alpha-synucleinopathy in centenarians, SP-positive and AS-positive lesions may involve a synergistic interaction.
- These results suggest that the internalization of alpha-synuclein is temperature-insensitive and occurs very rapidly via a mechanism distinct from normal endocytosis.
- While tyrosinase overexpression induced apoptosis, co-expression of wild type or A53T mutant human alpha-Synuclein with tyrosinase further exacerbated cell death.
- Synphilin-1A may contribute to neuronal degeneration in alpha-synuclein mutations and provides insights into the role of inclusion bodies in neurodegenerative disorders.
- These findings suggest that the high membrane ion permeability caused by mutant alpha-synuclein may contribute to the degeneration of neurons in PD.
- Frequency of spinal cord alpha-synuclein pathology in neurologically asymptomatic individuals older than 60 years of age.
- The composite Guam parkinsonism-dementia complex neuropathology profile of tau, alpha-synuclein and 8, 12-iso-iPF(2alpha)-VI isoprostane reported here more closely resembles that seen in other tauopathies including frontotemporal dementias (FTDs).
- C-terminal of alpha-synuclein is an important regulator of aggregation in vivo and will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders.
- The constant and abundant amyloid beta x-42 deposition in sporadic dementia with Lewy bodies suggests that alpha-synucleinopathy is also promoted by amyloid precursor protein dysfunction.
- Heat shock proteins may inhibit alpha-synuclein expression, accelerate alpha-synuclein degradation, thereby reducing the amount of alpha-synuclein protein and accordingly preventing its aggregation.
- S. cerevisiae model to evaluate misfolding, aggregation & toxicity-inducing ability of wild-type alpha-synuclein & mutants; results suggest toxic species in yeast are smaller than the visible aggregates & toxicity may involve membrane association
- Schizosaccharomyces pombe model that evaluates alpha-synuclein misfolding, aggregation & toxicity; results suggest that alpha-synuclein toxicity might be linked to its membrane binding capacity
- Results exclude high-affinity binding of FA molecules to specific alphaS sites and conclude alphaS bind to negatively charged membranes.
- the central hydrophobic region is critical for beta-sheet formation and the conformational alteration is the foundation of protein abnormal aggregation
- it is reported for the first time that transduced Tat-alpha-synuclein fusion protein protected against oxidative stress induced neuronal cell death by induction of HSP70 in vitro and in vivo
- These results suggest that in cells, alpha-syn is engaged in a fundamentally different mode of membrane interaction than the charge-dependent artificial membrane binding.
- While the toxicity of alpha-synuclein is supported in this review article, an alternate interpretation for a neuroprotective role of alpha-synuclein in Parkinson's disease is also emerging.
- the earliest defect following alphaSyn expression in yeast was a block in ER-to-Golgi vesicular trafficking; elevated expression of Rab1 protected against alpha-Synuclein-induced dopaminergic neuron loss in animal models of Parkinson Disease
- The selective susceptibility of nigral DA neurons is at least in part associated with factor(s) involved in handling of alpha-syn that is not shared by the VTA neurons.
- the important role of alpha-synuclein in neurotransmitter mobilization is not limited to dopaminergic terminals
- Preferential accumulation of normally produced Ser-129 phosphorylated alpha-synuclein is the key event responsible for the formation of Lewy bodies in various Lewy body diseases.
- suggest a novel physiological role for alpha-Syn in regulating SERT activity and may be of relevance in certain mental illnesses and in depression, in which SERT function is believed to be dysregulated.
- A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss Parkinsonian brains.
- alpha-synuclein levels are decreased in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease
- The results indicate that chronic overexpression of human alpha-synuclein led to abnormal pharmacological responses in mice.
- Results use data from multidimensional NMR spectroscopy to elucidate the molecular interactions between Abeta peptide and alpha-synuclein which may lead to onset of Lewy body dementia.
- the effect of Ca(2+) on the acidic tail conformation in lipid-bound alpha-synuclein, lipid interaction occurs via the N-terminal domain,then a Ca(2+)-triggered membrane association of the acidic tail leads to alpha-synuclein aggregation.
- findings indicate that increased expression of beta-synuclein protein results in a reduction of alpha-synuclein protein expression
- Targeting of alpha-synuclein to the nucleus promotes toxicity, but cytoplasmic sequestration is protective in cell culture & transgenic Drosophila; findings implicate nuclear alpha-synuclein in promoting nigrostriatal degeneration in Parkinson's disease
- These results indicate that the C-terminal portion of the membrane-bound alpha-syn is quite rigid and structured, at variance from current models of the membrane-bound protein.
- analysis of ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants
- Transgenic mice with the disease-associated A53T mutant alpha-syn show oligomeric alpha-syn in nondegenerating dopaminergic neurons that do contain insoluble alpha-syn. Intraneuronal dopamine levels modulate alpha-syn aggregation & inclusion formation.
- The binding of Hsp70 with PreAS only requires the substrate-binding subdomain, and the binding with AS nuclei requires the C-terminal lid subdomain as well.
- alpha-synuclein strongly stimulates human astrocytes as well as human U-373 MG astrocytoma cells to up-regulate both interleukin IL-6 and ICAM-1; mutated forms are more potent stimulators than wild-type
- Coexpression of the chaperone protein Hsp70, causes alpha-synuclein to adopt a different, open conformation, but Hsp70 does not alter alpha-synuclein-alpha-synuclein interactions.
- we focus on the role of the pre-synaptic protein alpha-synuclein in altering the proteasom based on the results emerging from experimental models showing a mechanistic chain of events between altered alpha-synuclein--REVIEW
- overexpression of alpha-synuclein apparently recapitulates several important features of brains with PD and dementia with Lewy bodies
- We conclude that the alpha-synuclein (G209A) gene mutation genotype should be considered in the differential diagnosis of dementia with Lewy bodies, particularly in patients with European ancestry and a family history of Parkinson's disease.
- the age-related increases in nigral alpha-synuclein were non-aggregated and strongly associated with age-related decreases in tyrosine hydroxylase
- MPTP-inducible, strictly alpha-Syn-dependent, increased formation of Tau, suggesting convergent overlapping pathways in the genesis of clinically divergent diseases such as Alzheimer and Parkinson disease.
- Genetic variations of the alpha-synuclein gene affect the development of sporadic PD.
- A primary physiological role of alpha-Syn may be to regulate the homeostasis of monoamines in synapses, through modulatory interactions of the protein with monoaminergic transporters.
- These studies suggest that the microtubule system is a potential target of alpha-syn, and impairment of this system might have impacts on neuronal structure and function.
- These findings demonstrate that alpha-synuclein acts as a potent inflammatory stimulator of microglial cells, and that inhibitors of such stimulation might be beneficial in the treatment of Parkinson's disease and other synucleinopathies.
- Truncated human alpha-synuclein is deleterious to the development and survival of nigral dopaminergic neurons in transgenic mice.
- Alpha-synuclein affects the micellar properties of polyunsaturated fatty acids, allowing docosahexaenoic acid to be present in a soluble rather than micellar form.
- Dopamine modulates differently the stability of protofibrils and fibrils composed of wild type or variants of alpha-syn (A30P and A53T) as probed by high hydrostatic pressure (HHP).
- under physiological conditions, alphaSyn exists as diverse conformational isomers which exhibit distinct propensities for aggregation and fibril formation
- No missense mutations or multiplications are found in the SNCA gene in patients with autosomal dominant Parkinson's disease.
- Gene dosage-dependent dysregulation of several genes important for dopaminergic phenotype in mice over-expressing wild-type human alpha-synuclein in substantia nigra at time points preceding neuronal cell death.
- The present study did not find any SNCA multiplications in a series of 58 pathologically confirmed MSA cases excluding this event as a common cause of MSA.
- Our results indicate that Rep1 locus may be in linkage disequilibrium (LD) with a mutation in the gene or itself could be a risk factor for SPD.
- These data show that alpha-synuclein over-expressed in human neural embryonic cells results in patterns of degeneration that in some cases match features of Parkinson Disease.
- This study found significantly lower levels of scna mRNA then control.
- Expression of alpha-synuclein may reflect the intricate role of alpha-synuclein in the pathogenesis of parkinson disease.
- variation in SNCA contributes to alcohol craving
- study shows aggregated oligomeric alpha-synuclein is internalized by dopaminergic cells & causes detrimental morphological changes prior to cell death; one mechanism by which it mediates cell death is disruption of tubulin polymerization into microtubule
- In a transgenic Drosophila model, aggregation of alpha-synuclein mediates toxicity to dopaminergic neurons in vivo.
- This newly identified poly-T polymorphism is a human-specific sequence; its length influences alpha-synuclein 126 expression levels; and, finally, it seems to exert a specific influence on normal aging.
- Given the concurrent loss of membrane binding by this alpha-synuclein mutation, we propose a membrane-bound functional complex with tau that might involve the actin cytoskeleton.
- Because stimulus-reward learning may be mediated by the basal ganglia and context learning may be related to the medial temporal lobe, our data raise the possibility that dopaminergic signals regulated by SNCA inversely affect these memory systems.
- These data strongly suggest that halpha-syn140m undergoes constitutive phosphorylation, and at least casein kinase-2 is involved in the phosphorylation.
- report of the first Korean Parkinson disease family with the Ala53Thr mutation in the SNCA gene that occurred on different haplotype from the original one in Greek and Italian families
- Circular dichroism and nuclear magnetic resonance spectroscopy illustrate that the E46K mutation results in subtle changes in the conformation of the monomeric protein both free in solution and in the presence of SDS micelles.
- The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish Parkinson's disease patients.
- The present investigation uncovers the detailed binding propensities between metals and alpha-synuclein and has biological implications in PD.
- Identificaton of a tilted peptide in alpha-synuclein, which could be involved in the toxicity induced during amyloidogenesis of alpha-synuclein.
- The plasma concentration displayed a median of 5.6 microg/L (range 2.1-19.4 microg/L) and there was no correlation with age and gender. Quantification of the plasma level of alpha-synuclein may be important as a biomarker for disease susceptibility.
- alpha-synuclein fibril structure analysis by site-directed spin labeling
- YPP1 suppresses lethality of A30P, but not of wild-type alpha-syn or the A53T mutant
- we develop a framework for thinking about alpha-synuclein in terms of initiating events and secondary processes that are required to trigger neuronal dysfunction and cell death--{REVIEW}
- alpha-Synuclein gene duplication is present in sporadic Parkinson disease
- The accumulation of alpha-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids.
- Data show that cortex in Parkinsonism-dementia complex is distinguished from Alzheimer's disease and progressive supranuclear palsy by its accumulation of abnormal alpha-synuclein and suggest that PDC is a synucleinopathy as well as a tauopathy.
- A comparison of the structural and dynamic properties of the free states of all three synucleins, is reported in order to shed light on differences that may help to explain their different propensities to aggregate.
- Tau and alpha-synuclein are involved in shared or converging pathways in pathogenesis of Parkinson's disease(PD). Tau inversion influences development of cognitive impairment and dementia in patients with idiopathic PD.
- Our data confirm the fatty acid binding properties of alpha-syn, and to a lesser extent beta-syn, but suggest that gamma-syn does not share this same characteristic.
- Further correlation studies are required in order to determine normal versus pathologic alpha-synuclein and how to detect such differences in clinical situations--{REVIEW}
- These results suggest that alpha-synuclein (1-120) renders dopaminergic cells more susceptible to stress, which may have important implications as to how this truncated protein might contribute to dopaminergic cell death in sporadic Parkinson's disease.
- The proapoptotic effects of alpha-synuclein might be mediated at least in part by the impairment of NF-kappaB signaling pathway which involves GSK3beta.
- alpha-Syn phosphorylation caused by FeCl2 is due to casein kinase 2 upregulation
- Cellular oligomerization of SNCA is determined by the interaction of oxidized catechols with a C-terminal sequence.
- oligodendroglial overexpression of alpha-synuclein may induce neuroinflammation related to nitrosive stress which is likely to contribute to neurodegeneration in multiple system atrophy
- Casein kinase 2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies
- Data suggest that genetic variability within the alpha-synuclein locus is associated with susceptibility to idiopathic Parkinson disease.
- alpha-Synuclein/dopamine transporter (DAT) protein complex formation accelerates DAT-mediated cellular dopamine (DA) uptake.
- Epitope mapping of an anti-alpha-synuclein monoclonal antibody has been performed.
- data suggest the lack of involvement of the SNCA promoter in the pathogenesis of dementia in Parkinson disease. Further studies in other populations are needed to confirm these results
- the assembly of mature alpha-synuclein fibrils is hierarchical: protofilaments --> protofibrils --> mature fibrils
- review:Isoform Synphilin-1A inclusions recruit both alpha-synuclein and synphilin-1. Aggregation of synphilin-1 and synphilin-1A seems to be protective to cells
- These data suggest that up-regulated alpha-synuclein expression inhibits the activity of vesicular monoamine transporter-2.
- The numbers of neuronal and glial inclusions, and the extent of neuritic changes, correlated with the PD stage (P < 0.001). These findings suggest that intrinsic neostriatal neurons degenerate through alphaS aggregation during PD progression.
- Data showed that that alphaB-crystallin interrupted alpha-synuclein aggregation at its earliest stages, most likely by binding to partially folded monomers and thereby preventing their aggregation into fibrillar structures.
- Importance of deposition of alpha-synuclein as well as its phosphorylation in the pathogenesis of alpha-synucleinopathies.
- Primary non-fibrillar and fibrillar alpha-synuclein aggregations occur in neurons in multiple system atrophy.[REVIEW]
- Oligomers and protofibrils of alpha-synuclein are cytotoxic, and that Lewy bodiess may represent a cytoprotective mechanism in Parkinson disease. [REVIEW]
- Results show that the channel activity, alpha-helical content, thermal stability of membrane-bound alpha-synuclein (alphaS) may have a role in the normal function and/or pathophysiology of the protein.
- the transcriptome and proteome of nitrated alpha-syn activated microglia, shown provide new potential insights into Parkinson disease mechanisms.
- The present data indicate that mutation in the alpha-synuclein gene may predispose the protein to dopamine-induced aggregation, thereby contributing to disease pathogenesis.
- We conclude that other environmental agents could play a key role in inducing programmed cell death in cells of PD patients with mutant alpha-synuclein.
- alpha-synuclein aggregation and alpha-synuclein toxicity are enhanced by Siah-1 mediated ubiquination
- monoubiquitylation by SIAH1 and SIAH2 represents a possible trigger event for alpha-synuclein aggregation and Lewy body formation
- alpha-synuclein levels are influenced by genetic variability in the promoter and 3' region of the SNCA gene in vivo.
- alpha-syn causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive
- phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease
- alpha-synuclein forms a high affinity lipid binding intermediate species during fibril formation. Oligomeric alpha-syn is known to be toxic & the high affinity binding species described here may correspond to a toxic species involved in Parkinson disease
- analysis of 20 gene products that reproducibly enhanced misfolding of alpha-synuclein over the course of aging in human and C. elegans
- More than 99% of alpha-synuclein in human blood is present in the peripheral blood cells, with the remainder in plasma.
- accumulation of alpha-synuclein might contribute to the pathogenesis of PD and other Lewy body diseases by promoting alterations in parkin and tubulin solubility
- We present a case of a SNCA gene duplication patient with Parkinson disease and dementia.
- alpha-synuclein promoter polymorphism and smoking was associated with Parkinson's disease
- No mutations were found in SNCA in Parkinson disease patients from Portugal.
- mitochondrial accumulated alpha-synuclein may interact with complex I and interfere with its functions.
- analysis of iron-induced pore-forming alpha-synuclein oligomers
- These data collectively indicate that the dimeric species of wild type alpha-synuclein and its mutants can bind and cause membrane perturbations.
- Identification of sequence determinants regulating fibrillation of amyloidogenic proteins may provide valuable information for designing peptide analog drugs to prevent protein amyloidosis.
- Results provide a structural analysis of the conformational characteristics of the unstructured peptide, alpha-synuclein.
- only aggregated forms of extracellular alpha-synuclein can be cleared by cell-mediated uptake and degradation, and this might represent a mechanism of preventing neurons from exposure to potentially toxic alpha-synuclein.
- These results indicate a possible role for alpha-synuclein in anxiety-like behaviours.
- These findings have implications not only for normal alpha-Syn function in TH regulation, but also for measuring cell loss that is associated with synucleinopathy.
- There is an increased risk of Parkinson disease with increasing synuclein-alpha (SNCA) dinucleotide repeat sequence variablility in a population exposed to pesticides.
- In this study 20-100% of alpha-synuclein-positive Lewy bodies in Parkinson disease patients contain LRRK2.
- These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by alpha-synuclein.
- Structural properties and propensities to form fibrils of alpha-synuclein at the initial stage were investigated.
- phosphorylation at Ser-129 increases the conformational flexibility of alpha-syn and inhibits its fibrillogenesis in vitro but does not perturb its membrane-bound conformation
- Alpha-Synucleinopathy is common in older people, and frequently associated with Alzheimer disease-type pathology. An unexpectedly high proportion with a cortical form of Lewy body disease was identified.
- link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism
- DJ-1 inactivation may promote alpha-syn aggregation and the related toxicity, and in this model HSP70 is involved in the antioxidant response and in the regulation of alpha-syn fibril formation
- alpha-synuclein reacts with tyrosinase and may have a role in Parkinson disease
- Data show that aberrant aggregation and Lewy body-like inclusion formation of alpha-synuclein in cytoplasm of HEK293 cell induced by overexpression of wild-type can be blocked by RNAi.
- Genotype-specific mean onset ages in Parkinson's disease displayed a trend of decreasing onset age with increasing allele size. Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD.
- Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and cognitive dysfunction is caused by SNCA duplication
- Transgenic alpha-synuclein accumulation contributes to alterations in neurogenesis by reducing the survival of neural precursor cells in the hippocampus via downregulation of Notch-1 expression.
- Data describe the characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR.
- CHIP preferentially recognizes and mediates degradation of toxic, oligomeric forms of alphaSyn
- The aggregation behavior of alpha- and beta-synuclein as well as a series of chimeric variants were compared by exploring the structural transitions that occur in the presence of a widely used lipid mimetic, sodium dodecyl sulfate (SDS).
- These results imply a direct role for alpha-synuclein in mitochondrial physiology, especially under pathological conditions, and in principle, link alpha-synuclein to other Parkinson's disease genes in regulating mitochondrial homeostasis.
- can modulate the function of microglia and influence inflammatory changes such as those seen in neurodegenerative disorders.
- These data provide novel explanations for the presence of hyperphosphorylated Ser129 alpha-syn in pathologic inclusions.
- decreased expression of Nurr1, which has been found in Parkinson's disease patients with Nurr1 mutations, was shown to transcriptionally increase alpha-synuclein expression
- human alphaSyn-overexpressing mice under Thy1 promoter (Thy1-alphaSyn) display alterations of colonic function
- Cu and Fe showed differential binding pattern toward alpha-synuclein as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis.
- These results suggest that microglia may be the major scavenger cells for extracellular alpha-synuclein aggregates in brain parenchyma, and that clearance may be regulated by the activation state of these cells.
- EPR spectroscopy, in conjunction with site-directed mutagenesis and isotopic labeling, was used to identify a minimum of four Cu2+ binding modes adopted by full length human alpha-synuclein between pH 5.0-7.4.
- Data suggest that tTG binds equally effective to wild-type and disease mutant alpha-synuclein variants .
- Solid-state NMR reveals structural differences between fibrils of wild-type and disease-related A53T mutant SNCA.
- There is evidence that a-synuclein aggregation is an early pathogenic event in LB disorders.
- alpha-synuclein toxicity may be dependent on the phosphorylation at Ser(129) that induces the UPRs, possibly triggered by the disturbed endoplasmic reticulum-Golgi trafficking
- ASYN and Lamp2a are developmentally regulated in parallel in cortical neuron cultures and in vivo in the central nervous system, and they physically interact
- FGF20 is associated with Parkinson's disease synergistically with SNCA.
- SNCA dosage is responsible for parkinsonism, autonomic dysfunction, and dementia observed within each family. Dysregulated expression of wild-type alpha-synuclein results in parkinsonism.
- Parkinson patients have markedly reduced levels of alpha-synuclein in cerebellum;this reduction is general, rather then correlates to the investigated polymorphisms in SNCA.
- non-phosphorylated alpha-synuclein carboxyl terminus pulled down protein complexes that were highly enriched for mitochondrial electron transport proteins, whereas alpha-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did not
- Endocytic pathway is involoved in alpha-synuclein-induced neurotoxicity in transgenic C. elegans.
- Plays an important role in the development of Parkinson's disease; insertion of a single point mutation is sufficient to generate age-related decline in specific motor performance in transgenic mice.
- Alpha-synuclein concentration is reduced in cerebrospinal fluid specimens from Parkinson disease, and possibly from subjects with dementia with Lewy bodies (DLB) when compared to neurological controls.
- Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration.
- These results suggest for the first time that variation of alpha-synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of alpha-synuclein and tau in neurodegeneration.
- Data suggest that the long-range intramolecular interactions between the N- and C-termini of alpha-synuclein are likely to be crucial to the fibrillation process.
- cathepsin D is the main lysosomal enzyme involved in alpha-synuclein degradation
- Overexpression of alpha-synuclein is sufficient to cause olfactory deficits in mice similar to that observed in patients with Parkinson's disease.
- Hsp104 likely protects dopaminergic neurons by antagonizing toxic alpha-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses
- Impairment of two lysosomal pathways, chaperone-mediated autophagy and macroautophagy, or of more general lysosomal function, may be an initiating factor in alpha-synuclein accumulation and sporadic Parkinson's disease pathogenesis.
- Data show that cardiac sympathetic denervation in Parkinson's disease links to SNCA duplication
- Baicalein-stabilized oligomers are beta-sheet-enriched according to CD and Fourier transform infrared spectroscopy analyses. From small-angle X-ray scattering and atomic force microscopy, the oligomers were characterized as compact globular species.
- Data show that the pathological deposits with antibodies against synuclein alpha has involved in the neuropathogenesis of the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam.
- The results indicate that the N-terminus of alphaS is essential for the PUFA-induced alphaS oligomerization.
- study identified a new family with SNCA duplication who developed parkinsonism, visual hallucination, and cognitive fluctuation
- replacement of glutamate by alanine at position 83 (E83A) abolishes the ability of dopamine to inhibit SNCA fibrillization
- Experiments using alpha-Syn deletion mutants indicated that interactions between the Hsp70 substrate binding domain and the alpha-Syn core hydrophobic region underlie assembly inhibition.
- These data show that overexpression of alpha-SYN alone, in the absence of overt neurodegeneration, is sufficient to trigger neuroinflammation with both microglial activation and stimulation of adaptive immunity.
- alpha-Syn accumulation causes complex cellular responses, which if persist may compromise cell viability.
- Results show that as well as having a number of effects on cellular events upstream of mitochondrial dysfunction, alpha-synuclein affects pathways downstream of superoxide production, possibly involving regulation of NOS activity.
- Alpha-Synuclein conformation affects its tyrosine-dependent oxidative aggregation
- These results demonstrate that 4-oxo-2-nonenal induced an almost complete conversion of monomeric alpha-synuclein into 40-80 nm wide and 6-8 nm high soluble beta-sheet-rich oligomers with a molecular weight of approximately 2000 kDa.
- This work quantitates the average nucleation and growth rate constants for alpha-synuclein aggregation and supports the hypothesis of the formation of a partially folded intermediate that promotes aggregation at higher temperatures or lower pH.
- study evaluated changes in whole genome expression in dopaminergic neuroblastoma cells caused by RNA interference of SNCA; expression of 361 genes was altered at least+/-1.5-fold with 82 up-regulated and 279 down-regulated
- The phenotype associated with SNCA multiplications correlates with the number of copies of the gene and provides the first insight into the mechanisms underlying SNCA multiplication.
- Effect of alpha synuclein (alphaSyn) on phospholipase D (PLD) activity might be due to increased endoplasmic reticulum-related stress associated with alphaSyn overexpression but is not likely due to specific or direct interaction between alphaSyn and PLD
- Inhibition of alpha-synuclein fibril assembly by small molecules: analysis using epitope-specific antibodies is reported.
- The molecular basis and clinical relevance of statistically decreased alphaSyn pathology in schizophrenic brain versus aged controls is unknown and needs further elucidation as will be necessary for its incidence and relevance in chronic affective diso..