synphilin 1


Gene Symbol: synphilin 1
Description: synuclein alpha interacting protein
Alias: SYPH1, Sph1, synphilin-1
Species: human
Products:     synphilin 1

Top Publications

  1. Smith W, Margolis R, Li X, Troncoso J, Lee M, Dawson V, et al. Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells. J Neurosci. 2005;25:5544-52 pubmed
    ..These results indicate that phosphorylation of alpha-synuclein at S129 may be important for the formation of inclusions in PD and related alpha synucleinopathies. ..
  2. Li X, Liu Z, Tamashiro K, Shi B, Rudnicki D, Ross C, et al. Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity. Neuroscience. 2010;165:455-62 pubmed publisher
  3. Kruger R. The role of synphilin-1 in synaptic function and protein degradation. Cell Tissue Res. 2004;318:195-9 pubmed
    ..The present article provides an overview of the current concepts of the role of synphilin-1 in synaptic function and protein degradation and in the molecular mechanisms leading to neurodegeneration in PD. ..
  4. Liani E, Eyal A, Avraham E, Shemer R, Szargel R, Berg D, et al. Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101:5500-5 pubmed
    ..In vitro experiments show that SIAH-2 monoubiquitylates alpha-synuclein. Further evidence that SIAH proteins may play a role in inclusion formation comes from the demonstration of SIAH immunoreactivity in Lewy bodies of PD patients. ..
  5. Maraganore D, Farrer M, Lesnick T, de Andrade M, Bower J, Hernandez D, et al. Case-control study of the alpha-synuclein interacting protein gene and Parkinson's disease. Mov Disord. 2003;18:1233-9 pubmed
    ..0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene. ..
  6. Nagano Y, Yamashita H, Takahashi T, Kishida S, Nakamura T, Iseki E, et al. Siah-1 facilitates ubiquitination and degradation of synphilin-1. J Biol Chem. 2003;278:51504-14 pubmed
    ..Siah-1 was found to abrogate the inhibitory effects of synphilin-1 on dopamine release. Such findings suggest that Siah-1 might play a role in regulation of synphilin-1 function. ..
  7. Avraham E, Szargel R, Eyal A, Rott R, Engelender S. Glycogen synthase kinase 3beta modulates synphilin-1 ubiquitylation and cellular inclusion formation by SIAH: implications for proteasomal function and Lewy body formation. J Biol Chem. 2005;280:42877-86 pubmed
  8. Kalia S, Lee S, Smith P, Liu L, Crocker S, Thorarinsdottir T, et al. BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron. 2004;44:931-45 pubmed
    ..This contrasts with the antideath functions ascribed to BAG family members and suggests a potential role for BAG5 in promoting neurodegeneration in sporadic PD through its functional interactions with parkin and Hsp70. ..
  9. Szargel R, Rott R, Engelender S. Synphilin-1 isoforms in Parkinson's disease: regulation by phosphorylation and ubiquitylation. Cell Mol Life Sci. 2008;65:80-8 pubmed
    ..Aggregation of synphilin-1 and synphilin-1A seems to be protective to cells. We now discuss several aspects of the neurobiology and pathology of synphilin-1 isoforms, focusing on possible implications for PD. ..

More Information


  1. Lee G, Tanaka M, Park K, Lee S, Kim Y, Junn E, et al. Casein kinase II-mediated phosphorylation regulates alpha-synuclein/synphilin-1 interaction and inclusion body formation. J Biol Chem. 2004;279:6834-9 pubmed
    ..These observations collectively indicate that a ubiquitous post-translational modification such as phosphorylation can regulate inclusion body formation in the context of alpha-synuclein and synphilin-1 interaction. ..
  2. Zaarur N, Meriin A, Gabai V, Sherman M. Triggering aggresome formation. Dissecting aggresome-targeting and aggregation signals in synphilin 1. J Biol Chem. 2008;283:27575-84 pubmed publisher
    ..We used synphilin 1, a protein implicated in Parkinson disease, as a model to study mechanisms of aggresome formation...
  3. Lee G, Junn E, Tanaka M, Kim Y, Mouradian M. Synphilin-1 degradation by the ubiquitin-proteasome pathway and effects on cell survival. J Neurochem. 2002;83:346-52 pubmed
    ..Accumulation of ubiquitinated synphilin-1 due to impaired clearance results in its aggregation as peri-nuclear inclusions and in poor cell survival. ..
  4. O Farrell C, Pickford F, Vink L, McGowan E, Cookson M. Sequence conservation between mouse and human synphilin-1. Neurosci Lett. 2002;322:9-12 pubmed
    ..Expression of mouse synphilin-1 across tissues is similar to its human counterpart and not limited to brain. The results show that the synphilin-1 sequence and expression patterns are conserved across species. ..
  5. Ribeiro C, Carneiro K, Ross C, Menezes J, Engelender S. Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by alpha-synuclein. J Biol Chem. 2002;277:23927-33 pubmed
    ..Our data indicated that synphilin-1 is a synaptic partner of alpha-synuclein, and it may mediate synaptic roles attributed to alpha-synuclein. ..
  6. Ito T, Niwa J, Hishikawa N, Ishigaki S, Doyu M, Sobue G. Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. J Biol Chem. 2003;278:29106-14 pubmed
  7. Xie Y, Zhou C, Zhou Z, Hong J, Che M, Fu Q, et al. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication. FASEB J. 2010;24:196-205 pubmed publisher
    ..Synphilin-1 (Sph1) is a novel alpha-Syn-interacting protein also present in the LBs...
  8. Alvarez Castelao B, Castaño J. Synphilin-1 inhibits alpha-synuclein degradation by the proteasome. Cell Mol Life Sci. 2011;68:2643-54 pubmed publisher
    ..Synphilin-1 inhibition of the proteasomal pathway of degradation of alpha-synuclein may help to understand the pathophysiological changes occurring in PD and other synucleinopathies. ..
  9. Marx F, Soehn A, Berg D, Melle C, Schiesling C, Lang M, et al. The proteasomal subunit S6 ATPase is a novel synphilin-1 interacting protein--implications for Parkinson's disease. FASEB J. 2007;21:1759-67 pubmed
    ..Our data suggest a direct interaction of synphilin-1 with the regulatory complex of the proteasome modulating proteasomal function. ..
  10. Tanji K, Tanaka T, Mori F, Kito K, Takahashi H, Wakabayashi K, et al. NUB1 suppresses the formation of Lewy body-like inclusions by proteasomal degradation of synphilin-1. Am J Pathol. 2006;169:553-65 pubmed
  11. Tanaka M, Kim Y, Lee G, Junn E, Iwatsubo T, Mouradian M. Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. J Biol Chem. 2004;279:4625-31 pubmed
  12. Soehn A, Franck T, Biskup S, Giaime E, Melle C, Rott R, et al. Periphilin is a novel interactor of synphilin-1, a protein implicated in Parkinson's disease. Neurogenetics. 2010;11:203-15 pubmed publisher
    ..Searching for mutations in the periphilin gene, we detected a K69E substitution in two patients of a PD family. Taken together, these findings support for the first time an involvement of periphilin in PD. ..
  13. Bandopadhyay R, De Silva R, Khan N, Graham E, Vaughan J, Engelender S, et al. No pathogenic mutations in the synphilin-1 gene in Parkinson's disease. Neurosci Lett. 2001;307:125-7 pubmed
    ..We analysed the intron 2 polymorphism for allelic association as it was conducive to rapid screening but observed no changes in frequency between Parkinson's disease cases and controls. ..
  14. Engelender S, Kaminsky Z, Guo X, Sharp A, Amaravi R, Kleiderlein J, et al. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat Genet. 1999;22:110-4 pubmed
    ..We found that alpha-synuclein interacts in vivo with synphilin-1 in neurons. Co-transfection of both proteins (but not control proteins) in HEK 293 cells yields cytoplasmic eosinophilic inclusions. ..
  15. Engelender S, Wanner T, Kleiderlein J, Wakabayashi K, Tsuji S, Takahashi H, et al. Organization of the human synphilin-1 gene, a candidate for Parkinson's disease. Mamm Genome. 2000;11:763-6 pubmed
    ..Because of its association with alpha-synuclein, synphilin-1 may be a candidate for involvement in Parkinson's disease or other related disorders. ..
  16. Lim K, Chew K, Tan J, Wang C, Chung K, Zhang Y, et al. Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci. 2005;25:2002-9 pubmed
    ..Our results suggest that parkin is a dual-function ubiquitin ligase and that K63-linked ubiquitination of synphilin-1 by parkin may be involved in the formation of Lewy body inclusions associated with PD. ..
  17. Marx F, Holzmann C, Strauss K, Li L, Eberhardt O, Gerhardt E, et al. Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet. 2003;12:1223-31 pubmed
  18. Chung K, Zhang Y, Lim K, Tanaka Y, Huang H, Gao J, et al. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001;7:1144-50 pubmed
    ..These results provide a molecular basis for the ubiquitination of Lewy-body-associated proteins and link parkin and alpha-synuclein in a common pathogenic mechanism through their interaction with synphilin-1. ..
  19. Liu J, Li T, Thomas J, Pei Z, Jiang H, Engelender S, et al. Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models. Hum Mol Genet. 2016;25:672-80 pubmed publisher
    ..Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role. ..
  20. Bandopadhyay R, Kingsbury A, Muqit M, Harvey K, Reid A, Kilford L, et al. Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition. Neurobiol Dis. 2005;20:401-11 pubmed
    ..We confirm that synphilin-1 and parkin are components of majority of LBs in Parkinson's disease and that both proteins are susceptible to proteasomal degradation. ..
  21. Ryo A, Togo T, Nakai T, Hirai A, Nishi M, Yamaguchi A, et al. Prolyl-isomerase Pin1 accumulates in lewy bodies of parkinson disease and facilitates formation of alpha-synuclein inclusions. J Biol Chem. 2006;281:4117-25 pubmed
    ..These results indicate that Pin1-mediated prolyl-isomerization plays a pivotal role in a post-translational modification pathway for alpha-synuclein aggregation and in the resultant Lewy body formations in PD. ..
  22. Lee H, Lee K, Im H. ?-Synuclein modulates neurite outgrowth by interacting with SPTBN1. Biochem Biophys Res Commun. 2012;424:497-502 pubmed publisher
    ..These results suggest that ?-synuclein modulates neurite outgrowth by interacting with cytoskeletal proteins such as SPTBN1. ..
  23. Esposito G, Ana Clara F, Verstreken P. Synaptic vesicle trafficking and Parkinson's disease. Dev Neurobiol. 2012;72:134-44 pubmed publisher
    ..This article reviews our current understanding for a role of causative PD genes in the SV cycle and speculates on the potential role of aberrant SV trafficking in the neurodegenerative cascade of PD. ..
  24. Miura H, Hashida K, Sudo H, Awa Y, Takarada Iemata M, Kokame K, et al. Deletion of Herp facilitates degradation of cytosolic proteins. Genes Cells. 2010;15:843-53 pubmed publisher
    ..These results suggest that ERAD molecule Herp may delay the degradation of cytosolic proteins at the ubiquitination step. ..
  25. Humbert J, Beyer K, Carrato C, Mate J, Ferrer I, Ariza A. Parkin and synphilin-1 isoform expression changes in Lewy body diseases. Neurobiol Dis. 2007;26:681-7 pubmed
    ..These findings suggest that parkin and synphilin-1 isoform expression changes play a significant role in the pathogenesis of LB diseases. ..
  26. Smith W, Smith M, Yang D, Choi P, Moghadam A, Li T, et al. CCK Response Deficiency in Synphilin-1 Transgenic Mice. PLoS ONE. 2015;10:e0142314 pubmed publisher
    ..These studies demonstrate that SP1 results in a CCK response deficiency that may contribute to the increased meal size and overall hyperphagia in synphillin-1 transgenic mice. ..
  27. Ghesquieres H, Slager S, Jardin F, Veron A, Asmann Y, Maurer M, et al. Genome-Wide Association Study of Event-Free Survival in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy. J Clin Oncol. 2015;33:3930-7 pubmed publisher
    ..2 and 6q21 with EFS and OS in patients with diffuse large B-cell lymphoma treated with immunochemotherapy, suggesting novel biology and the potential contribution of host genetics to the prognosis of this aggressive malignancy. ..
  28. Ikonomov O, Sbrissa D, Compton L, Kumar R, Tisdale E, Chen X, et al. The Protein Complex of Neurodegeneration-related Phosphoinositide Phosphatase Sac3 and ArPIKfyve Binds the Lewy Body-associated Synphilin-1, Preventing Its Aggregation. J Biol Chem. 2015;290:28515-29 pubmed publisher
    ..for brain-derived interactors of ArPIKfyve-Sac3 and unraveled the α-synuclein-interacting protein Synphilin-1 (Sph1) as a new component of the ArPIKfyve-Sac3 complex...
  29. Nagano Y, Yamashita H, Nakamura T, Takahashi T, Kondo E, Nakamura S. Lack of binding observed between human alpha-synuclein and Bcl-2 protein family. Neurosci Lett. 2001;316:103-7 pubmed
    ..In contrast, alpha-synuclein was observed to bind to synphilin-1. Although alpha-synuclein has been reported to bind to BAD, modification of alpha-synuclein might be required for such binding to occur. ..
  30. Satoh J, Kuroda Y. A putative polymorphic Val44Ala variation in the synphilin-1 gene is undetectable in Japanese sporadic Parkinson's disease patients. Eur J Neurol. 2002;9:15-8 pubmed
    ..All 116 subjects showed a homozygosity of Val at codon 44 in the synphilin-1 gene, suggesting that this SNP is unlikely to affect genetic susceptibility to sporadic PD in the Japanese population. ..
  31. Liu H, Wang Y, Sharma A, Mao R, Jiang N, Dun B, et al. Derivatives containing both coumarin and benzimidazole potently induce caspase-dependent apoptosis of cancer cells through inhibition of PI3K-AKT-mTOR signaling. Anticancer Drugs. 2015;26:667-77 pubmed publisher
  32. Zhou Z, Wu Y, Wang X, Han Y. The c-Abl inhibitor in Parkinson disease. Neurol Sci. 2017;38:547-552 pubmed publisher
    ..Therefore, we review the mechanism of the c-Abl inhibitor in PD and conclude that c-Abl inhibitors may be a potential treatment in PD and other neurodegenerative disease. ..
  33. Fu R, Liu S, Huang S, Chen H, Chen P, Lin Y, et al. Aberrant alternative splicing events in Parkinson's disease. Cell Transplant. 2013;22:653-61 pubmed publisher
    ..In this review, we highlight the relevance of aberrant AS in PD and discuss the use of an aberrant AS profile as a potential diagnostic or prognostic marker for PD and as a possible means of applying therapy. ..
  34. Ferreira Fernandes E, Esteves S, Korrodi Gregório L, Lüers G, Afreixo V, Fardilha M, et al. Synphilin-1A is a phosphoprotein phosphatase 1-interacting protein and affects PPP1 sorting to subcellular compartments. J Mol Neurosci. 2015;55:385-95 pubmed publisher
    Lewy bodies (LBs) are synphilin-1 (Sph1)-containing aggregates and histological hallmarks of Parkinson's disease...
  35. Dashtipour K, Tafreshi A, Adler C, Beach T, Chen X, Serrano G, et al. Hypermethylation of Synphilin-1, Alpha-Synuclein-Interacting Protein (SNCAIP) Gene in the Cerebral Cortex of Patients with Sporadic Parkinson's Disease. Brain Sci. 2017;7: pubmed publisher
    ..Hypomethylation of SNCAIP may function to protect against PD. The current results may suggest that the methylation status of SNCAIP could be useful as a marker in PD diagnosis and treatment and warrants further investigation. ..
  36. González Barbosa E, Mejía García A, Bautista E, Gonzalez F, Segovia J, Elizondo G. TCDD induces UbcH7 expression and synphilin-1 protein degradation in the mouse ventral midbrain. J Biochem Mol Toxicol. 2017;31: pubmed publisher
    ..In parallel, 2,3,7,8-tetrachlorodibenzo-p-dioxin promoted synphilin-1 degradation in an aryl hydrocarbon receptor-dependent way. ..
  37. Liu J, Li T, Yang D, Ma R, Moran T, Smith W. Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model. Int J Obes (Lond). 2012;36:1529-36 pubmed publisher
    ..These studies demonstrate that SP1 expression affects energy homeostasis in ways that enhance positive energy balance and provide a useful obesity model for future pathogenesis and therapeutic studies. ..
  38. Parelkar S, Cadena J, Kim C, Wang Z, Sugal R, Bentley B, et al. The parkin-like human homolog of Drosophila ariadne-1 (HHARI) can induce aggresome formation in mammalian cells and is immunologically detectable in Lewy bodies. J Mol Neurosci. 2012;46:109-21 pubmed publisher
    ..Taken together, these data suggest that HHARI, and perhaps other Parkin-like E3 ligases, may serve redundant roles for parkin in different cell types. ..
  39. Zaarur N, Xu X, Lestienne P, Meriin A, McComb M, Costello C, et al. RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. EMBO J. 2015;34:2363-82 pubmed publisher
    ..Finally, disassembly of protein aggregates was promoted by RuvbL. These data indicate that RuvbL complexes serve as chaperones in protein disaggregation. ..
  40. Poehler A, Xiang W, Spitzer P, May V, Meixner H, Rockenstein E, et al. Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment. Autophagy. 2014;10:2171-92 pubmed publisher
    ..These findings suggest that the major toxic role of SNCA is related to its extracellular species and further supports a protective role of intracellular SNCA aggregation. ..
  41. Geng X, Lou H, Wang J, Li L, Swanson A, Sun M, et al. α-Synuclein binds the K(ATP) channel at insulin-secretory granules and inhibits insulin secretion. Am J Physiol Endocrinol Metab. 2011;300:E276-86 pubmed publisher
    ..Synuclein might play similar roles in diabetes as it does in other degenerative diseases, including Alzheimer's and Parkinson's diseases. ..
  42. Soper J, Kehm V, Burd C, Bankaitis V, Lee V. Aggregation of ?-synuclein in S. cerevisiae is associated with defects in endosomal trafficking and phospholipid biosynthesis. J Mol Neurosci. 2011;43:391-405 pubmed publisher
    ..These data suggest new pathogenic mechanisms for ?-synuclein neurotoxicity. ..
  43. Dibenedetto D, Rossetti G, Caliandro R, Carloni P. A molecular dynamics simulation-based interpretation of nuclear magnetic resonance multidimensional heteronuclear spectra of ?-synuclein·dopamine adducts. Biochemistry. 2013;52:6672-83 pubmed publisher
    ..Hence, the performed analysis provides a rationale for the observed changes in chemical shifts in terms of direct contacts with the ligand and conformational changes in the protein. ..
  44. Sriram S, Li X, Ko H, Chung K, Wong E, Lim K, et al. Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin. Hum Mol Genet. 2005;14:2571-86 pubmed
  45. Mullin S, Schapira A. α-Synuclein and mitochondrial dysfunction in Parkinson's disease. Mol Neurobiol. 2013;47:587-97 pubmed publisher
    ..SNCA has a central role in these processes and manipulation of its expression, degradation and aggregation appear to be promising neuroprotective therapeutic targets. ..
  46. Eyal A, Szargel R, Avraham E, Liani E, Haskin J, Rott R, et al. Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients. Proc Natl Acad Sci U S A. 2006;103:5917-22 pubmed
    ..These findings suggest that synphilin-1A may contribute to neuronal degeneration in alpha-synucleinopathies and also provide important insights into the role of inclusion bodies in neurodegenerative disorders. ..
  47. Lee H, Kang S, Lee K, Im H. Human ?-synuclein modulates vesicle trafficking through its interaction with prenylated Rab acceptor protein 1. Biochem Biophys Res Commun. 2011;412:526-31 pubmed publisher
  48. Brudek T, Winge K, Rasmussen N, Bahl J, Tanassi J, Agander T, et al. Altered α-synuclein, parkin, and synphilin isoform levels in multiple system atrophy brains. J Neurochem. 2016;136:172-85 pubmed publisher
    ..The reported changes of isoform expression profiles suggest alterations in the regulation of transcription that may be important for aggregation of α-synuclein in the brain. ..
  49. Norris K, Hao R, Chen L, Lai C, Kapur M, Shaughnessy P, et al. Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling. J Biol Chem. 2015;290:13862-74 pubmed publisher
  50. Li T, Liu J, Smith W. Synphilin-1 binds ATP and regulates intracellular energy status. PLoS ONE. 2014;9:e115233 pubmed publisher
    ..Together, these data demonstrate that synphilin-1 binds and regulates the cellular energy molecule, ATP. These findings provide a molecular basis for understanding the actions of synphilin-1 in energy homeostasis. ..
  51. Bonin M, Marx F, Kautzmann S, Riess O, Kruger R. Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity. J Neural Transm (Vienna). 2008;115:941-58 pubmed publisher
    ..The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response. ..
  52. Chung K, Thomas B, Li X, Pletnikova O, Troncoso J, Marsh L, et al. S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function. Science. 2004;304:1328-31 pubmed
    ..The inhibition of parkin's ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in these disorders by impairing the ubiquitination of parkin substrates. ..
  53. Binolfi A, Rodriguez E, Valensin D, D Amelio N, Ippoliti E, Obal G, et al. Bioinorganic chemistry of Parkinson's disease: structural determinants for the copper-mediated amyloid formation of alpha-synuclein. Inorg Chem. 2010;49:10668-79 pubmed publisher
    ..These new findings are central to elucidate the mechanism through which the metal ion participates in the fibrillization of AS and represent relevant progress in the understanding of the bioinorganic chemistry of PD. ..
  54. Tanji K, Mori F, Kakita A, Zhang H, Kito K, Kamitani T, et al. Immunohistochemical localization of NUB1, a synphilin-1-binding protein, in neurodegenerative disorders. Acta Neuropathol. 2007;114:365-71 pubmed
    ..These findings indicate that the abnormal accumulation of NUB1 is specific for alpha-synucleinopathy lesions. However, yeast two-hybrid assay demonstrated that NUB1 did not directly interact with alpha-synuclein. ..
  55. Szargel R, Shani V, Abd Elghani F, Mekies L, Liani E, Rott R, et al. The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway. Hum Mol Genet. 2016;25:3476-3490 pubmed publisher
    ..Drugs that activate this pathway will provide a novel strategy to promote the clearance of damaged mitochondria in Parkinson's disease. ..
  56. Sato S, Chiba T, Sakata E, Kato K, Mizuno Y, Hattori N, et al. 14-3-3eta is a novel regulator of parkin ubiquitin ligase. EMBO J. 2006;25:211-21 pubmed
    ..Our findings indicate that 14-3-3eta is a regulator that functionally links parkin and alpha-SN. The alpha-SN-positive and 14-3-3eta-negative control of parkin activity sheds new light on the pathophysiological roles of parkin. ..
  57. Bellani S, Mescola A, Ronzitti G, Tsushima H, Tilve S, Canale C, et al. GRP78 clustering at the cell surface of neurons transduces the action of exogenous alpha-synuclein. Cell Death Differ. 2014;21:1971-83 pubmed publisher
  58. Jeffries M, Donica M, Baker L, Stevenson M, Annan A, Humphrey M, et al. Genome-wide DNA methylation study identifies significant epigenomic changes in osteoarthritic cartilage. Arthritis Rheumatol. 2014;66:2804-15 pubmed publisher
    ..Our data implicate epigenetic dysregulation of a host of genes and pathways in OA, including a number of OA susceptibility genes. Furthermore, we identified correlations between CpG methylation and histologic severity in OA. ..
  59. Myhre R, Klungland H, Farrer M, Aasly J. Genetic association study of synphilin-1 in idiopathic Parkinson's disease. BMC Med Genet. 2008;9:19 pubmed publisher
    ..However, marginal association of microsatellite alleles with idiopathic PD, within the chromosome 5q21 region, indicates further studies are warranted. ..
  60. Ihara M, Tomimoto H, Kitayama H, Morioka Y, Akiguchi I, Shibasaki H, et al. Association of the cytoskeletal GTP-binding protein Sept4/H5 with cytoplasmic inclusions found in Parkinson's disease and other synucleinopathies. J Biol Chem. 2003;278:24095-102 pubmed
    ..These data raise the possibility that Sept4 is involved in the formation of cytoplasmic inclusions as well as induction of cell death in alpha-synuclein-associated neurodegenerative disorders. ..
  61. Kalia L, Kalia S, Chau H, Lozano A, Hyman B, McLean P. Ubiquitinylation of ?-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5). PLoS ONE. 2011;6:e14695 pubmed publisher
    ..Thus, our results identify CHIP as an E3 ubiquitin ligase of ?-syn and suggest a novel function for BAG5 as a modulator of CHIP E3 ubiquitin ligase activity with implications for CHIP-mediated regulation of ?-syn oligomerization. ..
  62. Keyser R, Oppon E, Carr J, Bardien S. Identification of Parkinson's disease candidate genes using CAESAR and screening of MAPT and SNCAIP in South African Parkinson's disease patients. J Neural Transm (Vienna). 2011;118:889-97 pubmed publisher
    ..Mutation screening of MAPT and SNCAIP identified novel sequence variants in both genes and further studies are necessary to determine their possible functional consequences. ..
  63. Ramsey C, Giasson B. Identification and characterization of a novel endogenous murine parkin mutation. J Neurochem. 2010;113:402-17 pubmed publisher
  64. Casadei N, Pöhler A, Tomas Zapico C, Torres Peraza J, Schwedhelm I, Witz A, et al. Overexpression of synphilin-1 promotes clearance of soluble and misfolded alpha-synuclein without restoring the motor phenotype in aged A30P transgenic mice. Hum Mol Genet. 2014;23:767-81 pubmed publisher
  65. Yap T, Velayati A, Sidransky E, Lee J. Membrane-bound α-synuclein interacts with glucocerebrosidase and inhibits enzyme activity. Mol Genet Metab. 2013;108:56-64 pubmed publisher
    ..Importantly, the membrane-bound, α-helical form of α-synuclein is necessary for inhibition. This glucocerebrosidase interaction and inhibition likely contribute to the mechanism underlying GBA-associated parkinsonism. ..
  66. Ozansoy M, Basak A. The central theme of Parkinson's disease: ?-synuclein. Mol Neurobiol. 2013;47:460-5 pubmed publisher
  67. Jin H, Yamashita H, Nakamura T, Fukuba H, Takahashi T, Hiji M, et al. Synphilin-1 transgenic mice exhibit mild motor impairments. Neurosci Lett. 2008;445:12-7 pubmed publisher
    ..Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments. ..
  68. da Silva F, Coelho Cerqueira E, de Freitas M, Gonçalves D, Costa L, Follmer C. Vitamins K interact with N-terminus ?-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and ?-synuclein. Neurochem Int. 2013;62:103-12 pubmed publisher
    ..Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate ?-syn fibrillization in vitro. ..
  69. Hasegawa T, Baba T, Kobayashi M, Konno M, Sugeno N, Kikuchi A, et al. Role of TPPP/p25 on ?-synuclein-mediated oligodendroglial degeneration and the protective effect of SIRT2 inhibition in a cellular model of multiple system atrophy. Neurochem Int. 2010;57:857-66 pubmed publisher
    ..This apoptotic cell death was partly rescued by sirtuin 2 (SIRT2) inhibition. Together, our results provide further insight into the molecular pathogenesis of MSA and potential therapeutic approaches. ..
  70. Tsai Y, Riess O, Soehn A, Nguyen H. The Guanine nucleotide exchange factor kalirin-7 is a novel synphilin-1 interacting protein and modifies synphilin-1 aggregate transport and formation. PLoS ONE. 2012;7:e51999 pubmed publisher
    ..In summary, this is the first report demonstrating that kalirin-7 leads to the recruitment of synphilin-1 into aggresomes in a HDAC6-dependent manner and also links kalirin-7 to microtubule dynamics. ..
  71. Beyer K, Domingo Sàbat M, Humbert J, Carrato C, Ferrer I, Ariza A. Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body disease. Neurogenetics. 2008;9:163-72 pubmed publisher
    ..In conclusion, isoform-expression profiles in LB diseases represent additional evidence for the direct involvement of isoform-expression deregulation in the development of neurodegenerative disorders. ..
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    ..Our results suggest a novel function for synphilin-1A as a regulator of SIAH activity and formation of Lewy body-like inclusions. ..
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    ..These results indicate that the neuronal survival factor MEF2D is decreased in human and experimental PD, and this decrease is specifically associated with ?-synuclein accumulation and aggregation. ..