Snca

Summary

Gene Symbol: Snca
Description: synuclein, alpha
Alias: NACP, alpha-Syn, alphaSYN, alpha-synuclein, non-A beta component of AD amyloid, non-A4 component of amyloid
Species: mouse
Products:     Snca

Top Publications

  1. Reynolds A, Glanzer J, Kadiu I, Ricardo Dukelow M, Chaudhuri A, Ciborowski P, et al. Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. J Neurochem. 2008;104:1504-25 pubmed
    ..Taken together, the transcriptome and proteome of nitrated alpha-syn activated microglia, shown herein, provide new potential insights into disease mechanisms. ..
  2. Martinez Vicente M, Talloczy Z, Kaushik S, Massey A, Mazzulli J, Mosharov E, et al. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest. 2008;118:777-88 pubmed publisher
    ..As blockage of CMA increases cellular vulnerability to stressors, we propose that dopamine-induced autophagic inhibition could explain the selective degeneration of PD dopaminergic neurons. ..
  3. Sevlever D, Jiang P, Yen S. Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species. Biochemistry. 2008;47:9678-87 pubmed publisher
    ..Our findings suggest that upregulation of cathepsin D could be an additional therapeutic strategy to lessen alpha-synuclein burden in synucleinopathies. ..
  4. Roodveldt C, Labrador Garrido A, Gonzalez Rey E, Fernandez Montesinos R, Caro M, Lachaud C, et al. Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson's disease-linked mutants. PLoS ONE. 2010;5:e13481 pubmed publisher
  5. 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. ..
  6. Specht C, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci. 2001;2:11 pubmed
    ..Also, the findings exemplify unexpected complications that may arise during the study of transgenic models or inbred strains, in particular when combined with genome wide screening techniques. ..
  7. Burré J, Sharma M, Sudhof T. Systematic mutagenesis of ?-synuclein reveals distinct sequence requirements for physiological and pathological activities. J Neurosci. 2012;32:15227-42 pubmed publisher
  8. Giasson B, Duda J, Quinn S, Zhang B, Trojanowski J, Lee V. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron. 2002;34:521-33 pubmed
    ..These mice demonstrate that A53T alpha-synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal inclusions that cause neurodegeneration. ..
  9. Luk K, Kehm V, Zhang B, O BRIEN P, Trojanowski J, Lee V. Intracerebral inoculation of pathological ?-synuclein initiates a rapidly progressive neurodegenerative ?-synucleinopathy in mice. J Exp Med. 2012;209:975-86 pubmed publisher
    ..These findings open up new avenues for understanding the progression of PD and for developing novel therapeutics...
  10. Tehranian R, Montoya S, Van Laar A, Hastings T, Perez R. Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells. J Neurochem. 2006;99:1188-96 pubmed
    ..These novel findings further support a role for alpha-synuclein in dopamine homeostasis and may explain, at least in part, the selective vulnerability of dopamine neurons that occurs in PD. ..

Detail Information

Publications95

  1. Reynolds A, Glanzer J, Kadiu I, Ricardo Dukelow M, Chaudhuri A, Ciborowski P, et al. Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. J Neurochem. 2008;104:1504-25 pubmed
    ..Taken together, the transcriptome and proteome of nitrated alpha-syn activated microglia, shown herein, provide new potential insights into disease mechanisms. ..
  2. Martinez Vicente M, Talloczy Z, Kaushik S, Massey A, Mazzulli J, Mosharov E, et al. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest. 2008;118:777-88 pubmed publisher
    ..As blockage of CMA increases cellular vulnerability to stressors, we propose that dopamine-induced autophagic inhibition could explain the selective degeneration of PD dopaminergic neurons. ..
  3. Sevlever D, Jiang P, Yen S. Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species. Biochemistry. 2008;47:9678-87 pubmed publisher
    ..Our findings suggest that upregulation of cathepsin D could be an additional therapeutic strategy to lessen alpha-synuclein burden in synucleinopathies. ..
  4. Roodveldt C, Labrador Garrido A, Gonzalez Rey E, Fernandez Montesinos R, Caro M, Lachaud C, et al. Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson's disease-linked mutants. PLoS ONE. 2010;5:e13481 pubmed publisher
  5. 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. ..
  6. Specht C, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci. 2001;2:11 pubmed
    ..Also, the findings exemplify unexpected complications that may arise during the study of transgenic models or inbred strains, in particular when combined with genome wide screening techniques. ..
  7. Burré J, Sharma M, Sudhof T. Systematic mutagenesis of ?-synuclein reveals distinct sequence requirements for physiological and pathological activities. J Neurosci. 2012;32:15227-42 pubmed publisher
  8. Giasson B, Duda J, Quinn S, Zhang B, Trojanowski J, Lee V. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron. 2002;34:521-33 pubmed
    ..These mice demonstrate that A53T alpha-synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal inclusions that cause neurodegeneration. ..
  9. Luk K, Kehm V, Zhang B, O BRIEN P, Trojanowski J, Lee V. Intracerebral inoculation of pathological ?-synuclein initiates a rapidly progressive neurodegenerative ?-synucleinopathy in mice. J Exp Med. 2012;209:975-86 pubmed publisher
    ..These findings open up new avenues for understanding the progression of PD and for developing novel therapeutics...
  10. Tehranian R, Montoya S, Van Laar A, Hastings T, Perez R. Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells. J Neurochem. 2006;99:1188-96 pubmed
    ..These novel findings further support a role for alpha-synuclein in dopamine homeostasis and may explain, at least in part, the selective vulnerability of dopamine neurons that occurs in PD. ..
  11. Simon H, Saueressig H, Wurst W, Goulding M, O Leary D. Fate of midbrain dopaminergic neurons controlled by the engrailed genes. J Neurosci. 2001;21:3126-34 pubmed
    ..However, the engrailed genes control the survival of midbrain dopaminergic neurons in a gene dose-dependent manner. Our findings also suggest a link between engrailed and Parkinson's disease. ..
  12. Cabin D, Shimazu K, Murphy D, Cole N, Gottschalk W, McIlwain K, et al. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci. 2002;22:8797-807 pubmed
    ..These results reveal, for the first time, the normal function of endogenous alpha-synuclein in regulating synaptic vesicle mobilization at nerve terminals. ..
  13. Tsigelny I, Crews L, Desplats P, Shaked G, Sharikov Y, Mizuno H, et al. Mechanisms of hybrid oligomer formation in the pathogenesis of combined Alzheimer's and Parkinson's diseases. PLoS ONE. 2008;3:e3135 pubmed publisher
    ..The broader implications of such hybrid interactions might be important to the pathogenesis of other disorders of protein misfolding. ..
  14. Li W, West N, Colla E, Pletnikova O, Troncoso J, Marsh L, et al. Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations. Proc Natl Acad Sci U S A. 2005;102:2162-7 pubmed
    ..Collectively, our results indicate that the biology behind the generation and accumulation of alpha-SynDeltaC is likely to have relevance for the initiation and the progression of alpha-Syn aggregation in vivo. ..
  15. Volpicelli Daley L, Luk K, Patel T, Tanik S, Riddle D, Stieber A, et al. Exogenous ?-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron. 2011;72:57-71 pubmed publisher
  16. Kaul T, Credle J, Haggerty T, Oaks A, Masliah E, Sidhu A. Region-specific tauopathy and synucleinopathy in brain of the alpha-synuclein overexpressing mouse model of Parkinson's disease. BMC Neurosci. 2011;12:79 pubmed publisher
    ..Thus, tauopathy in PD may have a very restricted pattern of distribution. ..
  17. 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. ..
  18. Petrucelli L, O Farrell C, Lockhart P, Baptista M, Kehoe K, Vink L, et al. Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron. 2002;36:1007-19 pubmed
    ..Therefore, parkin and alpha-synuclein are linked by common effects on a pathway associated with selective cell death in catecholaminergic neurons. ..
  19. 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. ..
  20. Klivenyi P, Siwek D, Gardian G, Yang L, Starkov A, Cleren C, et al. Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis. 2006;21:541-8 pubmed
    ..These findings implicate alpha-synuclein as a modulator of oxidative damage, which has been implicated in neuronal death produced by MPTP and other mitochondrial toxins. ..
  21. Ikeda M, Kawarabayashi T, Harigaya Y, Sasaki A, Yamada S, Matsubara E, et al. Motor impairment and aberrant production of neurochemicals in human alpha-synuclein A30P+A53T transgenic mice with alpha-synuclein pathology. Brain Res. 2009;1250:232-41 pubmed publisher
    Missense point mutations, duplication and triplication in the alpha-synuclein (alphaSYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of alphaSYN pathologies, e...
  22. 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
    Mutations in the alpha-synuclein (alphaSYN) gene are associated with rare cases of familial Parkinson's disease, and alphaSYN is a major component of Lewy bodies and Lewy neurites...
  23. von Coelln R, Thomas B, Andrabi S, Lim K, Savitt J, Saffary R, et al. Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy. J Neurosci. 2006;26:3685-96 pubmed
  24. 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. ..
  25. 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. ..
  26. Hashimoto M, Hsu L, Rockenstein E, Takenouchi T, Mallory M, Masliah E. alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells. J Biol Chem. 2002;277:11465-72 pubmed
    ..Furthermore, interactions between alpha-synuclein and JIP-1b/IB1 may play a mutual role in the neuronal response to injury and neurodegeneration. ..
  27. 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. ..
  28. Gureviciene I, Gurevicius K, Tanila H. Role of alpha-synuclein in synaptic glutamate release. Neurobiol Dis. 2007;28:83-9 pubmed
    ..However, transgenic expression of A30P mutated or wild type alpha-synuclein does not appear to prevent endogenous mouse alpha-synuclein to carry out this function. ..
  29. Reyes J, Rey N, Bousset L, Melki R, Brundin P, Angot E. Alpha-synuclein transfers from neurons to oligodendrocytes. Glia. 2014;62:387-98 pubmed publisher
    ..Our findings support the hypothesis of a neuron-to-oligodendrocyte transfer of ?-syn, a mechanism that may play a crucial role in the progression and pathogenesis of MSA. ..
  30. Ninkina N, Papachroni K, Robertson D, Schmidt O, Delaney L, O Neill F, et al. Neurons expressing the highest levels of gamma-synuclein are unaffected by targeted inactivation of the gene. Mol Cell Biol. 2003;23:8233-45 pubmed
    ..Nerve injury led to similar changes in sensory function in wild-type and mutant mice. Taken together, our data suggest that like alpha-synuclein, gamma-synuclein is dispensable for the development and function of the nervous system. ..
  31. Al Wandi A, Ninkina N, Millership S, Williamson S, Jones P, Buchman V. Absence of alpha-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiol Aging. 2010;31:796-804 pubmed publisher
  32. Qiao L, Hamamichi S, Caldwell K, Caldwell G, Yacoubian T, Wilson S, et al. Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity. Mol Brain. 2008;1:17 pubmed publisher
    ..Our data identify a conserved CD function in ?-syn degradation and identify CD as a novel target for LB disease therapeutics. ..
  33. 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. ..
  34. Mak S, McCormack A, Manning Bog A, Cuervo A, Di Monte D. Lysosomal degradation of alpha-synuclein in vivo. J Biol Chem. 2010;285:13621-9 pubmed publisher
    ..It is conceivable that these neuronal mechanisms of protein clearance play an important role in neurodegenerative processes characterized by abnormal alpha-synuclein buildup. ..
  35. Rathke Hartlieb S, Kahle P, Neumann M, Ozmen L, Haid S, Okochi M, et al. Sensitivity to MPTP is not increased in Parkinson's disease-associated mutant alpha-synuclein transgenic mice. J Neurochem. 2001;77:1181-4 pubmed
    ..Mutations in the alpha-synuclein (alphaSYN ) gene are associated with rare cases of autosomal-dominant Parkinson's disease...
  36. Marsh J, Singh V, Jia Z, Forman Kay J. Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation. Protein Sci. 2006;15:2795-804 pubmed
  37. Dauer W, Kholodilov N, Vila M, Trillat A, Goodchild R, Larsen K, et al. Resistance of alpha -synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci U S A. 2002;99:14524-9 pubmed
  38. 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. ..
  39. Peng X, Peng X, Tehranian R, Dietrich P, Stefanis L, Perez R. Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. J Cell Sci. 2005;118:3523-30 pubmed
    ..Together the data reveal a functional interaction between alpha-synuclein and PP2A that leads to PP2A activation and underscores a key role for alpha-synuclein in protein phosphorylation. ..
  40. Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton M, Sudhof T. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010;329:1663-7 pubmed publisher
    ..Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging. ..
  41. Volles M, Lansbury P. Relationships between the sequence of alpha-synuclein and its membrane affinity, fibrillization propensity, and yeast toxicity. J Mol Biol. 2007;366:1510-22 pubmed
    ..We hypothesize that yeast toxicity is caused by synuclein binding directly to membranes at levels sufficient to non-specifically disrupt homeostasis. ..
  42. Yavich L, Tanila H, Vepsäläinen S, Jakala P. Role of alpha-synuclein in presynaptic dopamine recruitment. J Neurosci. 2004;24:11165-70 pubmed
    ..Reducing capacity of the storage pool in transgenic A30P mice led to paradoxical effects of l-dopa, which elevated dopamine release in response to single stimulation but decreased the refilling rate of the RRP. ..
  43. Stefanova N, Reindl M, Neumann M, Haass C, Poewe W, Kahle P, et al. Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol. 2005;166:869-76 pubmed
    ..Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies. ..
  44. Oaks A, Frankfurt M, Finkelstein D, Sidhu A. Age-dependent effects of A53T alpha-synuclein on behavior and dopaminergic function. PLoS ONE. 2013;8:e60378 pubmed publisher
    ..These findings highlight the involvement of the synuclein family of proteins and phosphorylation of Tau in the response to dopaminergic dysfunction of the nigrostriatal pathway. ..
  45. Kurz A, Wohr M, Walter M, Bonin M, Auburger G, Gispert S, et al. Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic vocalization. Neuroscience. 2010;166:785-95 pubmed publisher
    ..Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected. ..
  46. Golovko M, Murphy E. Brain prostaglandin formation is increased by alpha-synuclein gene-ablation during global ischemia. Neurosci Lett. 2008;432:243-7 pubmed publisher
    We have previously demonstrated that alpha-synuclein (Snca) gene ablation reduces brain arachidonic acid (20:4n-6) turnover rate in phospholipids through modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity...
  47. 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. ..
  48. Chadchankar H, Ihalainen J, Tanila H, Yavich L. Decreased reuptake of dopamine in the dorsal striatum in the absence of ?-synuclein. Brain Res. 2011;1382:37-44 pubmed publisher
    ..We show that ?-syn deletion produces significant adaptive changes in the striatal dopaminergic system via modulation of reuptake. ..
  49. Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher R, et al. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A. 2010;107:9879-84 pubmed publisher
  50. Nemani V, Lu W, Berge V, Nakamura K, Onoa B, Lee M, et al. Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron. 2010;65:66-79 pubmed publisher
    ..Increased levels of alpha-synuclein thus produce a specific, physiological defect in synaptic vesicle recycling that precedes detectable neuropathology. ..
  51. Chesselet M. In vivo alpha-synuclein overexpression in rodents: a useful model of Parkinson's disease?. Exp Neurol. 2008;209:22-7 pubmed
    ..The predictive value of all models of the disease, however, remains speculative in the absence of effective neuroprotective treatments for PD in humans. ..
  52. Neumann M, Kahle P, Giasson B, Ozmen L, Borroni E, Spooren W, et al. Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J Clin Invest. 2002;110:1429-39 pubmed
    ..The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions. ..
  53. Gao H, Kotzbauer P, Uryu K, Leight S, Trojanowski J, Lee V. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci. 2008;28:7687-98 pubmed publisher
    ..This study advances understanding of the role of neuroinflammation and abnormal SYN in the pathogenesis of PD and opens new avenues for the discovery of more effective therapies for PD. ..
  54. Totterdell S, Meredith G. Localization of alpha-synuclein to identified fibers and synapses in the normal mouse brain. Neuroscience. 2005;135:907-13 pubmed
  55. Tofaris G, Garcia Reitböck P, Humby T, Lambourne S, O Connell M, Ghetti B, et al. Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders. J Neurosci. 2006;26:3942-50 pubmed
    ..These findings suggest that the 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 and multiple system atrophy. ..
  56. Chandra S, Gallardo G, Fernandez Chacon R, Schlüter O, Sudhof T. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell. 2005;123:383-96 pubmed
  57. Lou H, Montoya S, Alerte T, Wang J, Wu J, Peng X, et al. Serine 129 phosphorylation reduces the ability of alpha-synuclein to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo. J Biol Chem. 2010;285:17648-61 pubmed publisher
    ..These findings extend our understanding of normal a-Syn biology and have implications for the dopamine dysfunction of Parkinson disease. ..
  58. 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 pubmed
    Because 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...
  59. Drolet R, Behrouz B, Lookingland K, Goudreau J. Mice lacking alpha-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration. Neurotoxicology. 2004;25:761-9 pubmed
  60. 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
    Elevated SNCA gene expression and intracellular accumulation of the encoded alpha-synuclein (aSyn) protein are associated with the development of Parkinson disease (PD)...
  61. Fauvet B, Mbefo M, Fares M, Desobry C, Michael S, Ardah M, et al. ?-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J Biol Chem. 2012;287:15345-64 pubmed publisher
    ..These results do not rule out the possibility that ?-syn becomes structured upon interaction with other proteins and/or biological membranes. ..
  62. Sousa V, Bellani S, Giannandrea M, Yousuf M, Valtorta F, Meldolesi J, et al. {alpha}-synuclein and its A30P mutant affect actin cytoskeletal structure and dynamics. Mol Biol Cell. 2009;20:3725-39 pubmed publisher
    ..Actin cytoskeletal disruption induced by the A30P mutant might alter various cellular processes and thereby play a role in the pathogenesis of neurodegeneration...
  63. Lim Y, Kehm V, Lee E, Soper J, Li C, Trojanowski J, et al. ?-Syn suppression reverses synaptic and memory defects in a mouse model of dementia with Lewy bodies. J Neurosci. 2011;31:10076-87 pubmed publisher
    ..Furthermore, when ?-syn expression was suppressed, we observed partial clearing of pre-existing ?-syn pathology and reversal of structural synaptic defects, resulting in an improvement in memory function. ..
  64. Rojanathammanee L, Murphy E, Combs C. Expression of mutant alpha-synuclein modulates microglial phenotype in vitro. J Neuroinflammation. 2011;8:44 pubmed publisher
  65. Emmanouilidou E, Elenis D, Papasilekas T, Stranjalis G, Gerozissis K, Ioannou P, et al. Assessment of ?-synuclein secretion in mouse and human brain parenchyma. PLoS ONE. 2011;6:e22225 pubmed publisher
    ..Our data suggest that ?-synuclein is physiologically secreted by neurons in vivo. This interstitial fluid pool of the protein may have a role in the propagation of synuclein pathology and progression of Parkinson's disease. ..
  66. Golovko M, Rosenberger T, Feddersen S, Faergeman N, Murphy E. Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids. J Neurochem. 2007;101:201-11 pubmed
    Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl)...
  67. Kuo Y, Li Z, Jiao Y, Gaborit N, Pani A, Orrison B, et al. Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes. Hum Mol Genet. 2010;19:1633-50 pubmed publisher
    ..familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes alpha-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates ..
  68. Schell H, Hasegawa T, Neumann M, Kahle P. Nuclear and neuritic distribution of serine-129 phosphorylated alpha-synuclein in transgenic mice. Neuroscience. 2009;160:796-804 pubmed publisher
    ..Mutations in the alpha-synuclein (alphaSYN) gene cause Parkinson's disease, often associated with dementia...
  69. Barcelo Coblijn G, Golovko M, Weinhofer I, Berger J, Murphy E. Brain neutral lipids mass is increased in alpha-synuclein gene-ablated mice. J Neurochem. 2007;101:132-41 pubmed
    Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that Snca deletion had on whole brain lipid composition...
  70. Specht C, Schoepfer R. Deletion of multimerin-1 in alpha-synuclein-deficient mice. Genomics. 2004;83:1176-8 pubmed
    A deletion of the murine Snca gene has been discovered in C57BL/6JOlaHsd, a population of the inbred strain C57BL/6J. We now characterize the exact nature of this deletion, Del(6)Snca1Slab...
  71. Robertson D, Schmidt O, Ninkina N, Jones P, Sharkey J, Buchman V. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. J Neurochem. 2004;89:1126-36 pubmed
  72. Bondar N, Boyarskikh U, Kovalenko I, Filipenko M, Kudryavtseva N. Molecular implications of repeated aggression: Th, Dat1, Snca and Bdnf gene expression in the VTA of victorious male mice. PLoS ONE. 2009;4:e4190 pubmed publisher
    ..The genes were Th, Dat1, Snca and Bdnf; the male mice were a group of animals that had each won 20 daily encounters in succession and a group of ..
  73. Rieker C, Dev K, Lehnhoff K, Barbieri S, Ksiazek I, Kauffmann S, et al. Neuropathology in mice expressing mouse alpha-synuclein. PLoS ONE. 2011;6:e24834 pubmed publisher
  74. Rockenstein E, Schwach G, Ingolic E, Adame A, Crews L, Mante M, et al. Lysosomal pathology associated with alpha-synuclein accumulation in transgenic models using an eGFP fusion protein. J Neurosci Res. 2005;80:247-59 pubmed
    ..Furthermore, the PDGFbeta-halpha-synuclein-eGFP tg model might be a valuable tool in testing new treatments for LBD in a fast and reliable manner. ..
  75. Sharma M, Burr J, S dhof T. CSP? promotes SNARE-complex assembly by chaperoning SNAP-25 during synaptic activity. Nat Cell Biol. 2011;13:30-9 pubmed publisher
    ..Thus, SNAP-25 function is maintained during rapid SNARE cycles by equilibrium between CSP?-dependent chaperoning and ubiquitin-dependent degradation, revealing unique protein quality-control machinery within the presynaptic compartment...
  76. Kurz A, Double K, Lastres Becker I, Tozzi A, Tantucci M, Bockhart V, et al. A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice. PLoS ONE. 2010;5:e11464 pubmed publisher
    ..age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA)...
  77. Gispert S, Del Turco D, Garrett L, Chen A, Bernard D, Hamm Clement J, et al. Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal dysfunction in the absence of aggregate formation. Mol Cell Neurosci. 2003;24:419-29 pubmed
    ..Transgenic animals expressing mutant alpha-synuclein may be a valuable model to assess specific aspects of the pathogenesis of synucleinopathies. ..
  78. Larsen K, Schmitz Y, Troyer M, Mosharov E, Dietrich P, Quazi A, et al. Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci. 2006;26:11915-22 pubmed
    ..We conclude that alpha-syn overexpression inhibits a vesicle "priming" step, after secretory vesicle trafficking to "docking" sites but before calcium-dependent vesicle membrane fusion. ..
  79. 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. ..
  80. 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. ..
  81. Hong L, Ko H, Gwag B, Joe E, Lee S, Kim Y, et al. The cDNA cloning and ontogeny of mouse alpha-synuclein. Neuroreport. 1998;9:1239-43 pubmed
    ..Levels of alpha-synuclein mRNA in these forebrain areas were nearly maximal at postnatal day 7 and remained relatively high until the adult stage. alpha-Synuclein mRNA was expressed in the liver transiently during embryogenesis. ..
  82. Liu C, Giasson B, Lewis K, Lee V, Demartino G, Thomas P. A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: implications for pathogenesis of Parkinson disease. J Biol Chem. 2005;280:22670-8 pubmed
    ..disease and other alpha-synucleinopathies are characterized by the deposition of intraneuronal alpha-synuclein (alphaSyn) inclusions...
  83. Stefanova N, Fellner L, Reindl M, Masliah E, Poewe W, Wenning G. Toll-like receptor 4 promotes ?-synuclein clearance and survival of nigral dopaminergic neurons. Am J Pathol. 2011;179:954-63 pubmed publisher
    ..The study supports TLR4 signaling as innate neuroprotective mechanism acting through clearance of ?-synuclein. ..
  84. Alvarez Fischer D, Henze C, Strenzke C, Westrich J, Ferger B, Höglinger G, et al. Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and alpha-synuclein-deleted mice. Exp Neurol. 2008;210:182-93 pubmed
    ..In summary, we propose that the striatal 6-OHDA model may be a valuable addition and/or alternative in genetically modified mice models used in the study of PD pathophysiology. ..
  85. Ekstrand M, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, et al. Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A. 2007;104:1325-30 pubmed
    ..These experiments demonstrate that respiratory chain dysfunction in DA neurons may be of pathophysiological importance in PD. ..