Genomes and Genes
Gene Symbol: alpha synuclein
Description: synuclein alpha
Alias: NACP, PARK1, PARK4, PD1, alpha-synuclein, I+/--synuclein, non A-beta component of AD amyloid, synuclein alpha-140, synuclein, alpha (non A4 component of amyloid precursor)
Products: alpha synuclein
- Spencer C, Plagnol V, Strange A, Gardner M, Paisan Ruiz C, Band G, et al. Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21. Hum Mol Genet. 2011;20:345-53 pubmed publisher..We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease. ..
- SimÃ³n SÃ¡nchez J, Schulte C, Bras J, Sharma M, Gibbs J, Berg D, et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet. 2009;41:1308-12 pubmed publisher..14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease. ..
- Thayanidhi N, Helm J, Nycz D, Bentley M, Liang Y, Hay J. Alpha-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell. 2010;21:1850-63 pubmed publisher..Finally, soluble alpha-synuclein A53T directly bound ER/Golgi SNAREs and inhibited SNARE complex assembly, providing a potential mechanism for toxic effects in the early secretory pathway. ..
- Al Chalabi A, DÃ¼rr A, Wood N, Parkinson M, Camuzat A, Hulot J, et al. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS ONE. 2009;4:e7114 pubmed publisher..035). We report a genetic association between MSA and alpha-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA. ClinicalTrials.gov NCT00211224. ..
- Mata I, Shi M, Agarwal P, Chung K, Edwards K, Factor S, et al. SNCA variant associated with Parkinson disease and plasma alpha-synuclein level. Arch Neurol. 2010;67:1350-6 pubmed publisher..This variant(s), tagged by rs356219, might act by upregulating SNCA expression in a dose-dependent manner. ..
- Siddiqui A, Chinta S, Mallajosyula J, Rajagopolan S, Hanson I, Rane A, et al. Selective binding of nuclear alpha-synuclein to the PGC1alpha promoter under conditions of oxidative stress may contribute to losses in mitochondrial function: implications for Parkinson's disease. Free Radic Biol Med. 2012;53:993-1003 pubmed publisher..This represents a novel role for alpha-synuclein as it relates to mitochondrial dysfunction in PD. ..
- Proukakis C, Houlden H, Schapira A. Somatic alpha-synuclein mutations in Parkinson's disease: hypothesis and preliminary data. Mov Disord. 2013;28:705-12 pubmed publisher..Further studies of brain-derived DNA are warranted and should include DNA from multiple regions and methods for detecting other types of genomic variation. ..
- Lesage S, Anheim M, Letournel F, Bousset L, Honoré A, Rozas N, et al. G51D ?-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol. 2013;73:459-71 pubmed publisher..We have identified a novel SNCA G51D mutation that causes a form of PD with unusual clinical, neuropathological, and biochemical features. ..
- Guo J, Covell D, Daniels J, Iba M, Stieber A, Zhang B, et al. Distinct ?-synuclein strains differentially promote tau inclusions in neurons. Cell. 2013;154:103-17 pubmed publisher..We speculate that distinct strains of pathological ?-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies. ..
- Rey N, Petit G, Bousset L, Melki R, Brundin P. Transfer of human ?-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol. 2013;126:555-73 pubmed publisher..Our results support the idea that ?-syn can transfer along neural pathways and thereby contribute to the progression of the ?-syn-related pathology. ..
- Rockenstein E, Nuber S, Overk C, Ubhi K, Mante M, Patrick C, et al. Accumulation of oligomer-prone ?-synuclein exacerbates synaptic and neuronal degeneration in vivo. Brain. 2014;137:1496-513 pubmed publisher..This oligomer-prone model might be useful for evaluating therapies directed at oligomer reduction. ..
- Dikiy I, Eliezer D. N-terminal acetylation stabilizes N-terminal helicity in lipid- and micelle-bound ?-synuclein and increases its affinity for physiological membranes. J Biol Chem. 2014;289:3652-65 pubmed publisher..Furthermore, the novel BOG-bound state of N-terminally acetylated ?-synuclein may serve as a model of partly helical membrane-bound intermediates with a role in ?-synuclein function and dysfunction. ..
- Bousset L, Pieri L, Ruiz Arlandis G, Gath J, Jensen P, Habenstein B, et al. Structural and functional characterization of two alpha-synuclein strains. Nat Commun. 2013;4:2575 pubmed publisher..Such strain differences may account for differences in disease progression in different individuals/cell types and/or types of synucleinopathies. ..
- Boassa D, Berlanga M, Yang M, Terada M, Hu J, Bushong E, et al. Mapping the subcellular distribution of ?-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: implications for Parkinson's disease pathogenesis. J Neurosci. 2013;33:2605-15 pubmed publisher..Our data support the conclusion that ?-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation. ..
- Fares M, Ait Bouziad N, Dikiy I, Mbefo M, Jovicic A, Kiely A, et al. The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of ?-synuclein, and enhances its secretion and nuclear localization in cells. Hum Mol Genet. 2014;23:4491-509 pubmed publisher..These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of ?-Syn aggregation. ..
- Ghosh D, Mondal M, Mohite G, Singh P, Ranjan P, Anoop A, et al. The Parkinson's disease-associated H50Q mutation accelerates ?-Synuclein aggregation in vitro. Biochemistry. 2013;52:6925-7 pubmed publisher..Understanding the aggregation mechanism of this H50Q mutant may help to establish the aggregation and phenotypic relationship of this novel mutant in PD. ..
- Oueslati A, Schneider B, Aebischer P, Lashuel H. Polo-like kinase 2 regulates selective autophagic ?-synuclein clearance and suppresses its toxicity in vivo. Proc Natl Acad Sci U S A. 2013;110:E3945-54 pubmed publisher..Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of ?-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies. ..
- George S, Rey N, Reichenbach N, Steiner J, Brundin P. ?-Synuclein: the long distance runner. Brain Pathol. 2013;23:350-7 pubmed publisher..We describe recent studies investigating cell-to-cell transfer of ?-synuclein and focus our review on the long-distance axonal transport of ?-synuclein along neurons. ..
- Sarafian T, Ryan C, Souda P, Masliah E, Kar U, Vinters H, et al. Impairment of mitochondria in adult mouse brain overexpressing predominantly full-length, N-terminally acetylated human Î±-synuclein. PLoS ONE. 2013;8:e63557 pubmed publisher..Overall the study showed that accumulation of full-length, N-terminally acetylated human Î±-synuclein was sufficient to disrupt brain mitochondrial function in adult mice. ..
- Paslawski W, Andreasen M, Nielsen S, Lorenzen N, Thomsen K, Kaspersen J, et al. High stability and cooperative unfolding of Î±-synuclein oligomers. Biochemistry. 2014;53:6252-63 pubmed publisher..The high stability of the Î±SN oligomer indicates that therapeutic strategies should aim to prevent the formation of or passivate rather than dissociate this cytotoxic species. ..
- Schildknecht S, Gerding H, Karreman C, Drescher M, Lashuel H, Outeiro T, et al. Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies. J Neurochem. 2013;125:491-511 pubmed publisher..Moreover, we hypothesize that ASYN may act physiologically as a catalytically regenerated scavenger of oxidants in healthy cells, thus performing an important protective role prior to the onset of disease or during aging. ..
- Masuda Suzukake M, Nonaka T, Hosokawa M, Oikawa T, Arai T, Akiyama H, et al. Prion-like spreading of pathological ?-synuclein in brain. Brain. 2013;136:1128-38 pubmed publisher..This is a new mouse model of sporadic ?-synucleinopathy and should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy. ..
- Foulds P, Diggle P, Mitchell J, Parker A, Hasegawa M, Masuda Suzukake M, et al. A longitudinal study on ?-synuclein in blood plasma as a biomarker for Parkinson's disease. Sci Rep. 2013;3:2540 pubmed publisher..012). Overall, we conclude that the plasma level of phosphorylated ?-synuclein has potential value as a diagnostic tool, whereas the level of total ?-synuclein could act as a surrogate marker for the progression of PD. ..
- Ulusoy A, Rusconi R, Pérez Revuelta B, Musgrove R, Helwig M, Winzen Reichert B, et al. Caudo-rostral brain spreading of ?-synuclein through vagal connections. EMBO Mol Med. 2013;5:1119-27 pubmed publisher..Thus, overexpression of human ?-synuclein in the lower brainstem is sufficient to induce its long-distance caudo-rostral propagation, recapitulating features of Parkinson's disease and mechanisms of disease progression. ..
- Prots I, Veber V, Brey S, Campioni S, Buder K, Riek R, et al. ?-Synuclein oligomers impair neuronal microtubule-kinesin interplay. J Biol Chem. 2013;288:21742-54 pubmed publisher..In summary, different ?-Syn species act divergently on the axonal transport machinery. These findings provide new insights into ?-Syn oligomer-driven neuritic pathology as one of the earliest events in synucleinopathies. ..
- Rutherford N, Moore B, Golde T, Giasson B. Divergent effects of the H50Q and G51D SNCA mutations on the aggregation of ?-synuclein. J Neurochem. 2014;131:859-67 pubmed publisher..G51D is the first SNCA mutation to show decreased ?-synuclein aggregation, suggesting a distinct disease mechanism to other SNCA mutations. ..
- Leftin A, Job C, Beyer K, Brown M. Solid-state ¹³C NMR reveals annealing of raft-like membranes containing cholesterol by the intrinsically disordered protein ?-Synuclein. J Mol Biol. 2013;425:2973-87 pubmed publisher..We propose this process is implicated in regulation of synaptic membrane fusion that may be altered by aggregation of ?S in Parkinson's disease. ..
- Ghosh D, Sahay S, Ranjan P, Salot S, Mohite G, Singh P, et al. The newly discovered Parkinson's disease associated Finnish mutation (A53E) attenuates Î±-synuclein aggregation and membrane binding. Biochemistry. 2014;53:6419-21 pubmed publisher..Further, A53E showed reduced membrane binding affinity compared to A53T and WT. The present study would help to delineate the role of A53E mutation in early onset PD pathogenesis. ..
- Guardia Laguarta C, Area Gomez E, Rüb C, Liu Y, Magrane J, Becker D, et al. ?-Synuclein is localized to mitochondria-associated ER membranes. J Neurosci. 2014;34:249-59 pubmed publisher..We believe that our results have far-reaching implications for both our understanding of ?-syn biology and the treatment of synucleinopathies. ..
- Basso E, Antas P, Marijanovic Z, Goncalves S, Tenreiro S, Outeiro T. PLK2 modulates ?-synuclein aggregation in yeast and mammalian cells. Mol Neurobiol. 2013;48:854-62 pubmed publisher..Our study supports a role for PLK2 in the generation of aSyn inclusions by a mechanism that does not depend directly on serine 129 phosphorylation. ..
- Boudes M, Uvin P, Pinto S, Voets T, Fowler C, Wenning G, et al. Bladder dysfunction in a transgenic mouse model of multiple system atrophy. Mov Disord. 2013;28:347-55 pubmed publisher..PLP-h?Syn mice recapitulate major urological symptoms of human MSA that may be linked to ?Syn-related central and peripheral neuropathology and can be further used as a preclinical model to decipher pathomechanisms of MSA...
- Irwin D, Lee V, Trojanowski J. Parkinson's disease dementia: convergence of ?-synuclein, tau and amyloid-? pathologies. Nat Rev Neurosci. 2013;14:626-36 pubmed publisher..An understanding of the relationships between these three distinct pathologies and their resultant clinical phenotypes is crucial for the development of effective disease-modifying treatments for PD and PDD. ..
- Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, et al. Triggering of inflammasome by aggregated ?-synuclein, an inflammatory response in synucleinopathies. PLoS ONE. 2013;8:e55375 pubmed publisher..Taken together, our data support the notion that fibrillar ?Syn, likely released by neuronal degeneration, acts as an endogenous trigger inducing a strong inflammatory response in PD. ..
- Singh P, Kotia V, Ghosh D, Mohite G, Kumar A, Maji S. Curcumin modulates ?-synuclein aggregation and toxicity. ACS Chem Neurosci. 2013;4:393-407 pubmed publisher..Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. ..
- Mysling S, Betzer C, Jensen P, Jorgensen T. Characterizing the dynamics of ?-synuclein oligomers using hydrogen/deuterium exchange monitored by mass spectrometry. Biochemistry. 2013;52:9097-103 pubmed publisher..This region has mainly been described in relation to membrane binding of ?SN, and structuring may be important in relation to disease. ..
- Paumier K, Sukoff Rizzo S, Berger Z, Chen Y, Gonzales C, Kaftan E, et al. Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease. PLoS ONE. 2013;8:e70274 pubmed publisher..Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments similar to PD patients and may provide useful endpoints for assessing novel therapeutic interventions for PD. ..
- Goncalves S, Outeiro T. Assessing the subcellular dynamics of alpha-synuclein using photoactivation microscopy. Mol Neurobiol. 2013;47:1081-92 pubmed publisher..Finally, we found that the molecular chaperone HSP70 accelerates the entry of aSyn into the nuclear compartment. ..
- Recasens A, Dehay B, Bove J, Carballo Carbajal I, Dovero S, Perez Villalba A, et al. Lewy body extracts from Parkinson disease brains trigger ?-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol. 2014;75:351-62 pubmed publisher..However, it remains uncertain whether the pathogenic effects of recombinant synthetic ?-synuclein may apply to PD-linked pathological ?-synuclein and occur in species closer to humans...
- Bender A, Desplats P, Spencer B, Rockenstein E, Adame A, Elstner M, et al. TOM40 mediates mitochondrial dysfunction induced by ?-synuclein accumulation in Parkinson's disease. PLoS ONE. 2013;8:e62277 pubmed publisher..Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in ?-Synucleinopathies. ..
- Chi Y, Armstrong G, Jones D, Eisenmesser E, Liu C. Residue histidine 50 plays a key role in protecting ?-synuclein from aggregation at physiological pH. J Biol Chem. 2014;289:15474-81 pubmed publisher..Histidine carries a partial positive charge at neutral pH, and so our result suggests that positively charged His-50 plays a role in protecting ?Syn from aggregation under physiological conditions. ..
- Wietek J, Haralampiev I, Amoussouvi A, Herrmann A, Stöckl M. Membrane bound ?-synuclein is fully embedded in the lipid bilayer while segments with higher flexibility remain. FEBS Lett. 2013;587:2572-7 pubmed publisher..We could show that while the entire helix is well embedded in the lipid bilayer, segments with a shallower penetration and supposable higher flexibility exist. ..
- Khalaf O, Fauvet B, Oueslati A, Dikiy I, Mahul Mellier A, Ruggeri F, et al. The H50Q mutation enhances ?-synuclein aggregation, secretion, and toxicity. J Biol Chem. 2014;289:21856-76 pubmed publisher..Together, our results provide novel insight into the mechanism by which this newly described PD-associated mutation may contribute to the pathogenesis of PD and related disorders...
- Moszczynska A, Saleh J, Zhang H, Vukusic B, Lee F, Liu F. Parkin disrupts the alpha-synuclein/dopamine transporter interaction: consequences toward dopamine-induced toxicity. J Mol Neurosci. 2007;32:217-27 pubmed..Moreover, we have found that parkin protects against DA-induced cell toxicity in dopaminergic SK-N-SH cells. These findings will help identify the role of these proteins in the etiology and/or maintenance of Parkinson's disease. ..
- Furukawa K, Matsuzaki Kobayashi M, Hasegawa T, Kikuchi A, Sugeno N, Itoyama Y, et al. Plasma membrane ion permeability induced by mutant alpha-synuclein contributes to the degeneration of neural cells. J Neurochem. 2006;97:1071-7 pubmed..These findings suggest that the high membrane ion permeability caused by mutant alpha-synuclein may contribute to the degeneration of neurons in PD. ..
- Shi M, Zabetian C, Hancock A, Ginghina C, Hong Z, Yearout D, et al. Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease. Neurosci Lett. 2010;480:78-82 pubmed publisher..In conclusion, unlike in cerebrospinal fluid, total DJ-1 or alpha-synuclein in plasma alone is not useful as biomarkers for Parkinson's disease diagnosis or progression/severity. ..
- Zaccai J, Brayne C, McKeith I, Matthews F, Ince P. Patterns and stages of alpha-synucleinopathy: Relevance in a population-based cohort. Neurology. 2008;70:1042-8 pubmed publisher..An unexpectedly high proportion with a cortical form of Lewy body disease was identified. ..
- Cullen V, Lindfors M, Ng J, Paetau A, Swinton E, Kolodziej P, et al. Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo. Mol Brain. 2009;2:5 pubmed publisher..We therefore postulate that CathD promotes 'synucleinase' activity, and that enhancing its function may lower aSyn concentrations in vivo. ..
- Fung K, Rorke L, Giasson B, Lee V, Trojanowski J. Expression of alpha-, beta-, and gamma-synuclein in glial tumors and medulloblastomas. Acta Neuropathol. 2003;106:167-75 pubmed..Of medulloblastomas, 76% have immunoreactivity for either alpha- or beta-synuclein or both; no immunoreactivity for gamma-synuclein is seen in medulloblastomas. ..
- Smith D, Tew D, Hill A, Bottomley S, Masters C, Barnham K, et al. Formation of a high affinity lipid-binding intermediate during the early aggregation phase of alpha-synuclein. Biochemistry. 2008;47:1425-34 pubmed publisher..Oligomeric alpha-syn is known to be toxic, and it is feasible that the high affinity binding species described here may correspond to a toxic species involved in PD. ..
- Yamakawa K, Izumi Y, Takeuchi H, Yamamoto N, Kume T, Akaike A, et al. Dopamine facilitates alpha-synuclein oligomerization in human neuroblastoma SH-SY5Y cells. Biochem Biophys Res Commun. 2010;391:129-34 pubmed publisher..Our data may contribute to the understanding of the mechanisms underlying alpha-synuclein oligomer formation and its suspected cytotoxicity toward dopaminergic neurons. ..
- Kalivendi S, Cunningham S, Kotamraju S, Joseph J, Hillard C, Kalyanaraman B. Alpha-synuclein up-regulation and aggregation during MPP+-induced apoptosis in neuroblastoma cells: intermediacy of transferrin receptor iron and hydrogen peroxide. J Biol Chem. 2004;279:15240-7 pubmed..We conclude that MPP(+)-induced iron signaling is responsible for intracellular oxidant generation, alpha-syn expression, proteasomal dysfunction, and apoptosis. Relevance to Parkinson's disease is discussed. ..
- Cao Z, Liu L, Wu P, Wang J. Structural and thermodynamics characters of isolated α-syn12 peptide: long-time temperature replica-exchange molecular dynamics in aqueous solution. Acta Biochim Biophys Sin (Shanghai). 2011;43:172-80 pubmed publisher..To our knowledge, this was the first report to study the isolated ?-syn12 peptide in water by T-REMD. ..
- Parihar M, Parihar A, Fujita M, Hashimoto M, Ghafourifar P. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci. 2008;65:1272-84 pubmed publisher..These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by alpha-synuclein. ..
- Carballo Carbajal I, Weber Endress S, Rovelli G, Chan D, Wolozin B, Klein C, et al. Leucine-rich repeat kinase 2 induces alpha-synuclein expression via the extracellular signal-regulated kinase pathway. Cell Signal. 2010;22:821-7 pubmed publisher..This pathway linking the two dominant PD genes LRRK2 and SNCA may offer an interesting target for drug therapy in both familial and sporadic disease. ..
- Mazzulli J, Armakola M, Dumoulin M, Parastatidis I, Ischiropoulos H. Cellular oligomerization of alpha-synuclein is determined by the interaction of oxidized catechols with a C-terminal sequence. J Biol Chem. 2007;282:31621-30 pubmed
- Kanazawa T, Adachi E, Orimo S, Nakamura A, Mizusawa H, Uchihara T. Pale neurites, premature ?-synuclein aggregates with centripetal extension from axon collaterals. Brain Pathol. 2012;22:67-78 pubmed publisher..This branching-oriented extension of ?S is related to its selective predisposition to systems with highly divergent axons, preferentially affected in PD, which may explain barely somatotopic manifestations of PD. ..
- Ikeuchi T, Kakita A, Shiga A, Kasuga K, Kaneko H, Tan C, et al. Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia. Arch Neurol. 2008;65:514-9 pubmed publisher..SNCA duplication results in the hyperaccumulation of phosphorylated alpha-synuclein in the brains of patients. ..
- Mollenhauer B, El Agnaf O, Marcus K, Trenkwalder C, Schlossmacher M. Quantification of ?-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med. 2010;4:683-99 pubmed publisher..We also provide specific information regarding standardized operating procedures for cerebrospinal fluid collection in PD biomarker research efforts. ..
- Ishii A, Nonaka T, Taniguchi S, Saito T, Arai T, Mann D, et al. Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies. FEBS Lett. 2007;581:4711-7 pubmed..Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies. ..
- Desplats P, Lee H, Bae E, Patrick C, Rockenstein E, Crews L, et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A. 2009;106:13010-5 pubmed publisher..These findings demonstrate the cell-to-cell transmission of alpha-synuclein aggregates and provide critical insights into the mechanism of pathological progression in PD and other proteinopathies. ..
- Lindersson E, Beedholm R, H jrup P, Moos T, Gai W, Hendil K, et al. Proteasomal inhibition by alpha-synuclein filaments and oligomers. J Biol Chem. 2004;279:12924-34 pubmed publisher..The inhibitory effect of amyloid aggregates may thus be amenable to modulation by endogenous chaperones and possibly accessible for therapeutic intervention...
- Lashuel H, Petre B, Wall J, Simon M, Nowak R, Walz T, et al. Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol. 2002;322:1089-102 pubmed..The formation of pore-like oligomeric structures may explain the membrane permeabilization activity of alpha-synuclein protofibrils. These structures may contribute to the pathogenesis of PD. ..
- Bellucci A, Navarria L, Zaltieri M, Falarti E, Bodei S, Sigala S, et al. Induction of the unfolded protein response by ?-synuclein in experimental models of Parkinson's disease. J Neurochem. 2011;116:588-605 pubmed publisher..These findings indicate that activation of the UPR pathway in the PD brain is associated with ?-synuclein accumulation occurring in part within the ER. ..
- Ohtake H, Limprasert P, Fan Y, Onodera O, Kakita A, Takahashi H, et al. Beta-synuclein gene alterations in dementia with Lewy bodies. Neurology. 2004;63:805-11 pubmed..Mutations in the beta-synuclein gene may predispose to DLB. ..
- Hong L, Simon J. Binding of Cu(II) to human alpha-synucleins: comparison of wild type and the point mutations associated with the familial Parkinson's disease. J Phys Chem B. 2009;113:9551-61 pubmed publisher..g., small oligomeric species, such as dimers and trimers) relative to WT and A53T. Thus, we propose that the high affinity site is attributed to the binding of Cu(II) to those small oligomeric species. ..
- Cole N, Murphy D, Lebowitz J, Di Noto L, Levine R, Nussbaum R. Metal-catalyzed oxidation of alpha-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments. J Biol Chem. 2005;280:9678-90 pubmed
- Chiba Falek O, Nussbaum R. Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system. Hum Mol Genet. 2001;10:3101-9 pubmed..been implicated in familial Parkinson's disease (PD) while certain polymorphic alleles at a microsatellite repeat, NACP-Rep1, located approximately 10 kb upstream of the gene, have been associated with sporadic PD...
- Yoshimoto M, Iwai A, Kang D, Otero D, Xia Y, Saitoh T. NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease amyloid, binds A beta and stimulates A beta aggregation. Proc Natl Acad Sci U S A. 1995;92:9141-5 pubmedb>NACP, a 140-amino acid presynaptic protein, is the precursor of NAC [the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease (AD) amyloid], a peptide isolated from and immunologically localized to brain amyloid of patients ..
- Banerjee K, Sinha M, Pham C, Jana S, Chanda D, Cappai R, et al. Alpha-synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: implications in Parkinson's disease. FEBS Lett. 2010;584:1571-6 pubmed publisher..The results are significant in view of the fact that alpha-synucleinopathy is involved in the pathogenesis of Parkinson's disease. ..
- Paleologou K, El Agnaf O. ?-Synuclein aggregation and modulating factors. Subcell Biochem. 2012;65:109-64 pubmed publisher..The current and most recent findings regarding the factors modulating a-syn aggregation process are discussed in detail. ..
- Crews L, Mizuno H, Desplats P, Rockenstein E, Adame A, Patrick C, et al. Alpha-synuclein alters Notch-1 expression and neurogenesis in mouse embryonic stem cells and in the hippocampus of transgenic mice. J Neurosci. 2008;28:4250-60 pubmed publisher..Together, these results suggest that accumulation of alpha-syn might impair survival of NPCs by interfering with the Notch signaling pathway. Similar mechanisms could be at play in PD and Lewy body disease. ..
- Ozawa T, Healy D, Abou Sleiman P, Ahmadi K, Quinn N, Lees A, et al. The alpha-synuclein gene in multiple system atrophy. J Neurol Neurosurg Psychiatry. 2006;77:464-7 pubmed..No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases. ..
- Bussell R, Eliezer D. Effects of Parkinson's disease-linked mutations on the structure of lipid-associated alpha-synuclein. Biochemistry. 2004;43:4810-8 pubmed..The potential implications of these results for the role of alphaS in PD are discussed. ..
- Murray I, Giasson B, Quinn S, Koppaka V, Axelsen P, Ischiropoulos H, et al. Role of alpha-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry. 2003;42:8530-40 pubmed..Thus, the carboxy-terminus of alpha-syn may regulate aggregation of full-length alpha-syn and determine the diameter of alpha-syn filaments. ..
- Inglis K, Chereau D, Brigham E, Chiou S, Schöbel S, Frigon N, et al. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem. 2009;284:2598-602 pubmed publisher..These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system. ..
- Kisos H, Pukaß K, Ben Hur T, Richter Landsberg C, Sharon R. Increased neuronal ?-synuclein pathology associates with its accumulation in oligodendrocytes in mice modeling ?-synucleinopathies. PLoS ONE. 2012;7:e46817 pubmed publisher..Hence, pathogenic mechanisms leading to elevated levels of ?-Syn in neurons underlie neuronal secretion and subsequent uptake of ?-Syn by oligodendrocytes in MSA. ..