Genomes and Genes
Gene Symbol: Snca
Description: synuclein alpha
Alias: alpha-synuclein, synuclein, alpha (non A4 component of amyloid precursor)
- Park J, Paik S, Jou I, Park S. Microglial phagocytosis is enhanced by monomeric alpha-synuclein, not aggregated alpha-synuclein: implications for Parkinson's disease. Glia. 2008;56:1215-23 pubmed publisher..This study indicates that alpha-syn can modulate the function of microglia and influence inflammatory changes such as those seen in neurodegenerative disorders. ..
- Paleologou K, Oueslati A, Shakked G, Rospigliosi C, Kim H, Lamberto G, et al. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci. 2010;30:3184-98 pubmed publisher..Together, our findings provide novel mechanistic insight into the role of phosphorylation at S87 and S129 in the pathogenesis of synucleinopathies and potential roles of phosphorylation in alpha-syn normal biology. ..
- Papachroni K, Ninkina N, Papapanagiotou A, Hadjigeorgiou G, Xiromerisiou G, Papadimitriou A, et al. Autoantibodies to alpha-synuclein in inherited Parkinson's disease. J Neurochem. 2007;101:749-56 pubmed..We hypothesise that these AAb could be involved in pathogenesis of the inherited form of PD. ..
- Winner B, Jappelli R, Maji S, Desplats P, Boyer L, Aigner S, et al. In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011;108:4194-9 pubmed publisher..e., E57K and E35K), whereas the ?-syn variants that form fibrils very quickly are less toxic. We show that ?-syn oligomers are toxic in vivo and that ?-syn oligomers might interact with and potentially disrupt membranes. ..
- Angot E, Steiner J, Lema Tome C, Ekström P, Mattsson B, Bjorklund A, et al. Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo. PLoS ONE. 2012;7:e39465 pubmed publisher..Our new model system could be used to test compounds that inhibit cell-to-cell transfer of ?-synuclein and therefore might retard progression of Parkinson neuropathology. ..
- Uryu K, Giasson B, Longhi L, Martinez D, Murray I, Conte V, et al. Age-dependent synuclein pathology following traumatic brain injury in mice. Exp Neurol. 2003;184:214-24 pubmed..This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies. ..
- Ben Gedalya T, Loeb V, Israeli E, Altschuler Y, Selkoe D, Sharon R. Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic. 2009;10:218-34 pubmed publisher..We suggest that alphaS and PUFAs normally function in endocytic mechanisms and are specifically involved in SV recycling upon neuronal stimulation. ..
- Fortin D, Nemani V, Voglmaier S, Anthony M, Ryan T, Edwards R. Neural activity controls the synaptic accumulation of alpha-synuclein. J Neurosci. 2005;25:10913-21 pubmed..Furthermore, the dispersion of alpha-synuclein is graded with respect to stimulus intensity. Neural activity thus controls the normal function of alpha-synuclein at the nerve terminal and may influence its role in PD. ..
- Austin S, Floden A, Murphy E, Combs C. Alpha-synuclein expression modulates microglial activation phenotype. J Neurosci. 2006;26:10558-63 pubmed..This has direct ramifications for the contribution of microglia to the pathophysiology of disease, particularly in familial cases linked to altered alpha-synuclein expression. ..
- Duka T, Rusnak M, Drolet R, Duka V, Wersinger C, Goudreau J, et al. Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism. FASEB J. 2006;20:2302-12 pubmed
- Gorbatyuk O, Li S, Nash K, Gorbatyuk M, Lewin A, Sullivan L, et al. In vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration. Mol Ther. 2010;18:1450-7 pubmed publisher..Our data show that alpha-syn plays an important role in the rat SNc and suggest that both up- and downregulation of wild-type alpha-syn expression increase the risk of nigrostriatal pathology. ..
- Greten Harrison B, Polydoro M, Morimoto Tomita M, Diao L, Williams A, Nie E, et al. Î±Î²Î³-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proc Natl Acad Sci U S A. 2010;107:19573-8 pubmed publisher..Our results demonstrate that synucleins contribute importantly to the long-term operation of the nervous system and that alterations in their physiological function could contribute to the development of Parkinson's disease. ..
- Czapski G, Gassowska M, Wilkaniec A, Cieslik M, Adamczyk A. Extracellular alpha-synuclein induces calpain-dependent overactivation of cyclin-dependent kinase 5 in vitro. FEBS Lett. 2013;587:3135-41 pubmed publisher..Cdk5 and calpain inhibitors prevented ASN-evoked cell death. Our findings, indicating the participation of Cdk5 in ASN toxicity, provide new insight into how extracellular ASN may trigger dopaminergic cell dysfunction in PD. ..
- Polymeropoulos M, Lavedan C, Leroy E, Ide S, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997;276:2045-7 pubmed..This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder. ..
- Kazmierczak A, Strosznajder J, Adamczyk A. alpha-Synuclein enhances secretion and toxicity of amyloid beta peptides in PC12 cells. Neurochem Int. 2008;53:263-9 pubmed publisher..Our results indicate that alpha-synuclein enhances the release and toxicity of amyloid beta leading to nitric oxide mediated irreversible mitochondria dysfunction and caspase-dependent programmed cell death. ..
- Gorbatyuk O, Li S, Sullivan L, Chen W, Kondrikova G, Manfredsson F, et al. The phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease. Proc Natl Acad Sci U S A. 2008;105:763-8 pubmed publisher..This suggests possible new therapeutic targets for Parkinson Disease. ..
- Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kösel S, et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 1998;18:106-8 pubmed
- Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, et al. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science. 2000;287:1265-9 pubmed..These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions. ..
- Luk K, Mills I, Trojanowski J, Lee V. Interactions between Hsp70 and the hydrophobic core of alpha-synuclein inhibit fibril assembly. Biochemistry. 2008;47:12614-25 pubmed publisher..Furthermore, our findings suggest that this critical step in Parkinson's disease pathogenesis may be subject to modulation by a common molecular chaperone. ..
- Kragh C, Lund L, Febbraro F, Hansen H, Gai W, El Agnaf O, et al. Alpha-synuclein aggregation and Ser-129 phosphorylation-dependent cell death in oligodendroglial cells. J Biol Chem. 2009;284:10211-22 pubmed publisher..Hence, the model predicts that both Ser-129 phosphorylation and aggregation control the toxic alpha-syn pathway in oligodendroglial cells and may represent therapeutic intervention points in multiple system atrophy. ..
- Ding T, Lee S, Rochet J, Lansbury P. Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes. Biochemistry. 2002;41:10209-17 pubmed..Thus, abnormal membrane permeabilization may be a pathogenic mechanism in PD. ..
- Nielsen M, Vorum H, Lindersson E, Jensen P. Ca2+ binding to alpha-synuclein regulates ligand binding and oligomerization. J Biol Chem. 2001;276:22680-4 pubmed..This suggests that Ca(2+) ions may both participate in normal alpha-synuclein functions in the nerve terminal and exercise pathological effects involved in the formation of Lewy bodies. ..
- Daher J, Abdelmotilib H, Hu X, Volpicelli Daley L, Moehle M, Fraser K, et al. Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates Î±-Synuclein Gene-induced Neurodegeneration. J Biol Chem. 2015;290:19433-44 pubmed publisher..These results demonstrate that pharmacological inhibition of LRRK2 is well tolerated for a 4-week period of time in rats and can counteract dopaminergic neurodegeneration caused by acute Î±-synuclein overexpression. ..
- Yan J, Yuan Y, Gao Y, Huang J, Ma K, Gao Y, et al. Overexpression of human E46K mutant ?-synuclein impairs macroautophagy via inactivation of JNK1-Bcl-2 pathway. Mol Neurobiol. 2014;50:685-701 pubmed publisher..Our findings may shed light on the potential roles of mutant ?-synuclein in the pathogenesis of PD. ..
- Gassowska M, Czapski G, Pajak B, Cieslik M, Lenkiewicz A, Adamczyk A. Extracellular ?-synuclein leads to microtubule destabilization via GSK-3?-dependent Tau phosphorylation in PC12 cells. PLoS ONE. 2014;9:e94259 pubmed publisher..Concluding, extracellular ASN is involved in GSK-3?-dependent Tau hyperphosphorylation, which leads to microtubule destabilization. GSK-3? inhibition may be an effective strategy for protecting against ASN-induced cytotoxicity. ..
- Phillips R, Billingsley C, Powley T. Macrophages are unsuccessful in clearing aggregated alpha-synuclein from the gastrointestinal tract of healthy aged Fischer 344 rats. Anat Rec (Hoboken). 2013;296:654-69 pubmed publisher..Thus, accumulating deposits of insoluble ?-SYNC in the wall of the GI tract may contribute, especially when compounded by disease or inflammation, to the age-associated neuropathies in the gut that compromise GI function. ..
- Liu J, Zhou Y, Wang Y, Fong H, Murray T, Zhang J. Identification of proteins involved in microglial endocytosis of alpha-synuclein. J Proteome Res. 2007;6:3614-27 pubmed
- Xu Z, Cawthon D, McCastlain K, Slikker W, Ali S. Selective alterations of gene expression in mice induced by MPTP. Synapse. 2005;55:45-51 pubmed..Future studies will focus on gene expression of other pathways that may be affected by MPTP treatment and investigation of gene expression in specific cell types in vivo using LCM technology. ..
- Mori F, Inenaga C, Yoshimoto M, Umezu H, Tanaka R, Takahashi H, et al. Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells. Acta Neuropathol. 2002;103:145-51 pubmed..No beta- or gamma-synuclein immunoreactivity was found in those cells. These results indicate that in the PNS, alpha-synuclein is a useful marker of Schwann cells and that it is not involved in tumorigenesis. ..
- Roy A, Pahan K. Ankyrin repeat and BTB/POZ domain containing protein-2 inhibits the aggregation of alpha-synuclein: implications for Parkinson's disease. FEBS Lett. 2013;587:3567-74 pubmed publisher..Finally, the absence of BPOZ-2 in ?-synuclein expressing neuronal populations of MPTP-intoxicated mouse and primate nigra indicates that the suppression of BPOZ-2 could be involved in the accumulation of ?-synuclein protein. ..
- BÃ¶ttner M, Fricke T, MÃ¼ller M, Barrenschee M, Deuschl G, Schneider S, et al. Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system. Brain Res. 2015;1614:51-9 pubmed publisher..The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age. ..
- Dermentzaki G, Paschalidis N, Politis P, Stefanis L. Complex Effects of the ZSCAN21 Transcription Factor on Transcriptional Regulation of Î±-Synuclein in Primary Neuronal Cultures and in Vivo. J Biol Chem. 2016;291:8756-72 pubmed publisherSynuclein, a presynaptic neuronal protein encoded by the SNCA gene, is strongly implicated in Parkinson disease (PD)...
- Jinn S, Drolet R, Cramer P, Wong A, Toolan D, Gretzula C, et al. TMEM175 deficiency impairs lysosomal and mitochondrial function and increases Î±-synuclein aggregation. Proc Natl Acad Sci U S A. 2017;114:2389-2394 pubmed publisher..Taken together, data from these studies suggest that TMEM175 plays a direct and critical role in lysosomal and mitochondrial function and PD pathogenesis and highlight this ion channel as a potential therapeutic target for treating PD. ..
- Lücke C, Gantz D, Klimtchuk E, Hamilton J. Interactions between fatty acids and alpha-synuclein. J Lipid Res. 2006;47:1714-24 pubmed..Binding to negatively charged membranes, however, appears to be an intrinsic property of alphaS that is most likely related to its physiological role(s) in the cell. ..
- Kubo S, Nemani V, Chalkley R, Anthony M, Hattori N, Mizuno Y, et al. A combinatorial code for the interaction of alpha-synuclein with membranes. J Biol Chem. 2005;280:31664-72 pubmed
- Choi D, Kim Y, Kim Y, Joh T, Beal M, Kim Y. Role of matrix metalloproteinase 3-mediated alpha-synuclein cleavage in dopaminergic cell death. J Biol Chem. 2011;286:14168-77 pubmed publisher..The results strongly indicate that MMP3 digestion of ?-synuclein in DA neurons plays a pivotal role in the progression of PD through modulation of ?-synuclein in aggregation, LB formation, and neurotoxicity. ..
- Ellis C, Murphy E, Mitchell D, Golovko M, Scaglia F, Barceló Coblijn G, et al. Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol. 2005;25:10190-201 pubmed..In mice lacking alpha-synuclein (Snca-/-), total brain steady-state mass of the mitochondria-specific phospholipid, cardiolipin, is reduced 22% and its ..
- Malatynska E, Pinhasov A, Crooke J, Horowitz D, Brenneman D, Ilyin S. Levels of mRNA coding for alpha-, beta-, and gamma-synuclein in the brains of newborn, juvenile, and adult rats. J Mol Neurosci. 2006;29:269-77 pubmed..The revealed pattern and dynamics of changes in the levels of mRNA coding for synucleins would support the conclusion for an important role of these molecules during development and the aging process. ..
- May V, Ettle B, Poehler A, Nuber S, Ubhi K, Rockenstein E, et al. ?-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy. Neurobiol Aging. 2014;35:2357-68 pubmed publisher..Taken together, efficacious induction of OPC maturation may open the window to restore glial and neuronal function in MSA. ..
- Kahle P, Neumann M, Ozmen L, Muller V, Odoy S, Okamoto N, et al. Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model. Am J Pathol. 2001;159:2215-25 pubmed..In conclusion, the specific accumulation of detergent-insoluble alpha-SYN in transgenic mice recapitulates a pivotal feature of human LB diseases. ..
- Wang Z, Udeshi N, O Malley M, Shabanowitz J, Hunt D, Hart G. Enrichment and site mapping of O-linked N-acetylglucosamine by a combination of chemical/enzymatic tagging, photochemical cleavage, and electron transfer dissociation mass spectrometry. Mol Cell Proteomics. 2010;9:153-60 pubmed publisher..Using this strategy, eight O-GlcNAc sites were mapped from a tau-enriched sample from rat brain. Sites of GlcNAcylation were characterized on important neuronal proteins such as tau, synucleins, and methyl CpG-binding protein 2. ..
- Zhang L, Zhang C, Zhu Y, Cai Q, Chan P, Ueda K, et al. Semi-quantitative analysis of alpha-synuclein in subcellular pools of rat brain neurons: an immunogold electron microscopic study using a C-terminal specific monoclonal antibody. Brain Res. 2008;1244:40-52 pubmed publisher..The relative high level of mitochondrial alpha-Syn in hippocampus, striatum and substantia nigral neurons may have special pathophysiological significance, which deserves further investigation. ..
- Liu Y, Fallon L, Lashuel H, Liu Z, Lansbury P. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002;111:209-18 pubmed..Thus, the ligase activity as well as the hydrolase activity of UCH-L1 may play a role in proteasomal protein degradation, a critical process for neuronal health. ..
- Golovko M, Rosenberger T, Faergeman N, Feddersen S, Cole N, Pribill I, et al. Acyl-CoA synthetase activity links wild-type but not mutant alpha-synuclein to brain arachidonate metabolism. Biochemistry. 2006;45:6956-66 pubmedBecause alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca-/- mice...
- Chandra S, Fornai F, Kwon H, Yazdani U, Atasoy D, Liu X, et al. Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc Natl Acad Sci U S A. 2004;101:14966-71 pubmed..These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function. ..
- Narayanan V, Guo Y, Scarlata S. Fluorescence studies suggest a role for alpha-synuclein in the phosphatidylinositol lipid signaling pathway. Biochemistry. 2005;44:462-70 pubmed..Given that Ca(2+) and dopamine regulation are mediated through PLCbeta and G protein signals, our results suggest that alpha-synuclein may play a role in inositol phospholipid signaling. ..
- JEANNOTTE A, McCarthy J, Redei E, Sidhu A. Desipramine modulation of alpha-, gamma-synuclein, and the norepinephrine transporter in an animal model of depression. Neuropsychopharmacology. 2009;34:987-98 pubmed publisher..These results are the first to implicate alpha-Syn or gamma-Syn in the pathophysiology of depression and suggest that targeting synucleins may provide a new therapeutic option for depression...
- Golebiewska U, Scarlata S. High pressure promotes alpha-synuclein aggregation in cultured neuronal cells. FEBS Lett. 2015;589:3309-12 pubmed publisher..These studies suggest that pressure promotes release of Î±-synuclein from protein partners promoting its oligomerization. ..
- Wersinger C, Jeannotte A, Sidhu A. Attenuation of the norepinephrine transporter activity and trafficking via interactions with alpha-synuclein. Eur J Neurosci. 2006;24:3141-52 pubmed
- Jellinger K. Lewy body/alpha-synucleinopathy in schizophrenia and depression: a preliminary neuropathological study. Acta Neuropathol. 2009;117:423-7 pubmed publisher..Among chronic affective disorders, according to our small cohort, the incidence of Lewy-pathology in LLD appears to be comparable to a healthy elderly population, whereas its occurence in BD is to be elucidated. ..
- Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L. Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem. 2008;283:23542-56 pubmed publisher..These results indicate that CMA and macroautophagy are important pathways for WT ASYN degradation in neurons and underline the importance of CMA as degradation machinery in the nervous system. ..
- Ma K, Song L, Long W, Yuan Y, Zhang Y, Song X, et al. Deletion in exon 5 of the SNCA gene and exposure to rotenone leads to oligomerization of ?-synuclein and toxicity to PC12 cells. Brain Res Bull. 2013;90:127-31 pubmed publisher..When exposed to rotenone, these cell lines which over expressed exon 5-lacking form of ?-syn isoforms showed the formation of oligomeric species and toxicity to PC12 cells. ..
- 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. ..
- Li J, Henning Jensen P, Dahlstrom A. Differential localization of alpha-, beta- and gamma-synucleins in the rat CNS. Neuroscience. 2002;113:463-78 pubmed..Gamma-synuclein appears to be present in both cholinergic and catecholaminergic regions, but very weak in the forebrain. ..
- Lee E, Woo M, Moon P, Baek M, Choi I, Kim W, et al. Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol. 2010;185:615-23 pubmed publisher..Furthermore, our findings suggest that modulation of the activities of MMPs and/or PAR-1 may provide a new therapeutic strategy for Parkinson's disease. ..
- Gorbatyuk O, Li S, Nguyen F, Manfredsson F, Kondrikova G, Sullivan L, et al. ?-Synuclein expression in rat substantia nigra suppresses phospholipase D2 toxicity and nigral neurodegeneration. Mol Ther. 2010;18:1758-68 pubmed publisher..Our data also demonstrate that it is possible to use viral-mediated gene transfer to study gene interactions in vivo. ..
- Febbraro F, Sahin G, Farran A, Soares S, Jensen P, Kirik D, et al. Ser129D mutant alpha-synuclein induces earlier motor dysfunction while S129A results in distinctive pathology in a rat model of Parkinson's disease. Neurobiol Dis. 2013;56:47-58 pubmed publisher..Our data show that changes in the S129 residue of ?-synuclein influence the rate of pathology and neurodegeneration, with an overall deleterious effect of exchanging S129 to a residue mimicking its phosphorylated state. ..
- Renella R, Schlehe J, Selkoe D, Williams D, LaVoie M. Genetic deletion of the GATA1-regulated protein ?-synuclein reduces oxidative stress and nitric oxide synthase levels in mature erythrocytes. Am J Hematol. 2014;89:974-7 pubmed publisher..While specific ?-synuclein (SNCA) mutations are known to cause autosomal dominant familial Parkinson's disease, its wild-type function remains under ..
- Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, et al. beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc Natl Acad Sci U S A. 2001;98:12245-50 pubmed..Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated. ..
- Song J, Lu J, Liu L, Chen L, Durairajan S, Yue Z, et al. HMGB1 is involved in autophagy inhibition caused by SNCA/?-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B. Autophagy. 2014;10:144-54 pubmed publisherb>SNCA/?-synuclein and its rare mutations are considered as the culprit proteins in Parkinson disease (PD). Wild-type (WT) SNCA has been shown to impair macroautophagy in mammalian cells and in transgenic mice...
- Meloni G, Vasak M. Redox activity of ?-synuclein-Cu is silenced by Zn?-metallothionein-3. Free Radic Biol Med. 2011;50:1471-9 pubmed publisher..These studies provide new insights into the bioinorganic chemistry of PD. ..
- Boyer F, Dreyer J. Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats. Eur J Neurosci. 2007;26:2764-76 pubmed..This suggests that targeting alpha-synuclein function could provide new therapeutic strategies to treat cocaine abuse, for which there is no available treatment. ..
- Yin G, Lopes da Fonseca T, Eisbach S, Anduaga A, Breda C, Orcellet M, et al. ?-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner. Neurobiol Dis. 2014;70:149-61 pubmed publisher..Our study provides novel mechanistic insights into the interplay of the GTPase Rab8a and ?S cytotoxicity, and underscores the therapeutic potential of targeting this interaction. ..
- Lo Bianco C, Shorter J, Regulier E, Lashuel H, Iwatsubo T, Lindquist S, et al. Hsp104 antagonizes alpha-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease. J Clin Invest. 2008;118:3087-97 pubmed publisher..Hsp104 likely protects dopaminergic neurons by antagonizing toxic alpha-synuclein assemblies and might have therapeutic potential for PD and other neurodegenerative amyloidoses. ..
- Malkiewicz K, Mohammed R, Folkesson R, Winblad B, Szutowski M, Benedikz E. Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain. Toxicol Lett. 2006;161:152-8 pubmed
- Plotegher N, Kumar D, Tessari I, Brucale M, Munari F, Tosatto L, et al. The chaperone-like protein 14-3-3? interacts with human ?-synuclein aggregation intermediates rerouting the amyloidogenic pathway and reducing ?-synuclein cellular toxicity. Hum Mol Genet. 2014;23:5615-29 pubmed publisher..Our findings constitute a first step in elucidating the molecular mechanism of aS/14-3-3? interaction and in understanding the critical aggregation step at which 14-3-3? has the potential to rescue aS-induced cellular toxicity. ..
- Yu S, Li X, Liu G, Han J, Zhang C, Li Y, et al. Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience. 2007;145:539-55 pubmed..This finding indicates an important physiological function of this molecule in the nuclei of brain neurons, which deserves further investigations. ..
- Zach S, Bueler H, Hengerer B, Gillardon F. Predominant neuritic pathology induced by viral overexpression of alpha-synuclein in cell culture. Cell Mol Neurobiol. 2007;27:505-15 pubmed..Our results indicate that these cell culture models may represent an early phase of PD reflecting pathologic neuritic alterations before significant neuronal cell loss occurs. ..
- Liu S, Fa M, Ninan I, Trinchese F, Dauer W, Arancio O. Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII. Eur J Neurosci. 2007;25:3583-96 pubmed..Thus, our results suggest that NO, cGMP, GMP-dependent protein kinase and calmodulin-dependent protein kinase II play a key role in the redistribution of alpha-synuclein during plasticity. ..
- Westerlund M, Ran C, Borgkvist A, Sterky F, Lindqvist E, Lundströmer K, et al. Lrrk2 and alpha-synuclein are co-regulated in rodent striatum. Mol Cell Neurosci. 2008;39:586-91 pubmed publisher..Because striatal Lrrk2 and alpha-synuclein levels were not changed by dopamine depletion, we conclude that Lrrk2 and alpha-synuclein mRNA levels are possibly co-regulated, but they are not influenced by striatal dopamine levels. ..
- Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, et al. alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999;19:5782-91 pubmed..The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases. ..
- Kahle P, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A, et al. Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain. J Neurosci. 2000;20:6365-73 pubmed..Thus, mutant [A30P]alphaSYN does not fail to be transported to synapses, but its transgenic overexpression apparently leads to abnormal cellular accumulations. ..
- Zhou Z, Kerk S, Xiong G, Lim T. Dopamine auto-oxidation aggravates non-apoptotic cell death induced by over-expression of human A53T mutant alpha-synuclein in dopaminergic PC12 cells. J Neurochem. 2009;108:601-10 pubmed publisher..Taken together, we concluded that auto-oxidation of endogenous DA aggravates non-apoptotic cell death induced by over-expression of human mutant A53T alpha-syn in PC12 cells. ..
- Herrera F, Outeiro T. ?-Synuclein modifies huntingtin aggregation in living cells. FEBS Lett. 2012;586:7-12 pubmed publisher..Our results support the idea that co-aggregation of aggregation-prone proteins can contribute to the histopathology of neurodegenerative disorders...
- Golovko M, Faergeman N, Cole N, Castagnet P, Nussbaum R, Murphy E. Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding. Biochemistry. 2005;44:8251-9 pubmed..Thus, alpha-synuclein has effects on 16:0 uptake and metabolism similar to those of an FABP, but unlike FABP, it does not directly bind 16:0; hence, the mechanism underlying these effects is different from that of a classical FABP. ..
- Wakabayashi K, Hayashi S, Yoshimoto M, Kudo H, Takahashi H. NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson's disease brains. Acta Neuropathol. 2000;99:14-20 pubmed..The number of inclusions was correlated with the severity of nigral neuronal loss. These findings indicate that abnormal accumulation of NACP/alpha-synuclein in glial cells is a pathological feature of PD related to its progression. ..