DC Field | Value | Language |
---|---|---|
dc.contributor.author | Panicker, Nikhil | ko |
dc.contributor.author | Sarkar, Souvarish | ko |
dc.contributor.author | Harischandra, Dilshan S. | ko |
dc.contributor.author | Neal, Matthew | ko |
dc.contributor.author | Kam, Tae-In | ko |
dc.contributor.author | Jin, Huajun | ko |
dc.contributor.author | Saminathan, Hariharan | ko |
dc.contributor.author | Langley, Monica | ko |
dc.contributor.author | Charli, Adhithiya | ko |
dc.contributor.author | Samidurai, Manikandan | ko |
dc.contributor.author | Rokad, Dharmin | ko |
dc.contributor.author | Ghaisas, Shivani | ko |
dc.contributor.author | Pletnikova, Olga | ko |
dc.contributor.author | Dawson, Valina L. | ko |
dc.contributor.author | Dawson, Ted M. | ko |
dc.contributor.author | Anantharam, Vellareddy | ko |
dc.contributor.author | Kanthasamy, Anumantha G. | ko |
dc.contributor.author | Kanthasamy, Arthi | ko |
dc.date.accessioned | 2023-05-04T07:00:44Z | - |
dc.date.available | 2023-05-04T07:00:44Z | - |
dc.date.created | 2023-05-04 | - |
dc.date.created | 2023-05-04 | - |
dc.date.issued | 2019-06 | - |
dc.identifier.citation | JOURNAL OF EXPERIMENTAL MEDICINE, v.216, no.6, pp.1411 - 1430 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10203/306622 | - |
dc.description.abstract | Persistent microglia-mediated neuroinflammation is a major pathophysiological contributor to the progression of Parkinson's disease (PD), but the cell-signaling mechanisms governing chronic neuroinflammation are not well understood. Here, we show that Fyn kinase, in conjunction with the class B scavenger receptor CD36, regulates the microglial uptake of aggregated human alpha-synuclein (alpha Syn), which is the major component of PD-associated Lewy bodies. alpha Syn can effectively mediate LPS-independent priming and activation of the microglial NLRP3 inflammasome. Fyn kinase regulates both of these processes; it mediates PKC delta-dependent NF-kappa B-p65 nuclear translocation, leading to inflammasome priming, and facilitates alpha Syn import into microglia, contributing to the generation of mitochondrial reactive oxygen species and consequently to inflammasome activation. In vivo experiments using A53T and viral-alpha Syn overexpression mouse models as well as human PD neuropathological results further confirm the role of Fyn in NLRP3 inflammasome activation. Collectively, our study identifies a novel Fyn-mediated signaling mechanism that amplifies neuroinflammation in PD. | - |
dc.language | English | - |
dc.publisher | ROCKEFELLER UNIV PRESS | - |
dc.title | Fyn kinase regulates misfolded alpha-synuclein uptake and NLRP3 inflammasome activation in microglia | - |
dc.type | Article | - |
dc.identifier.wosid | 000470082900015 | - |
dc.identifier.scopusid | 2-s2.0-85067214404 | - |
dc.type.rims | ART | - |
dc.citation.volume | 216 | - |
dc.citation.issue | 6 | - |
dc.citation.beginningpage | 1411 | - |
dc.citation.endingpage | 1430 | - |
dc.citation.publicationname | JOURNAL OF EXPERIMENTAL MEDICINE | - |
dc.identifier.doi | 10.1084/jem.20182191 | - |
dc.contributor.localauthor | Kam, Tae-In | - |
dc.contributor.nonIdAuthor | Panicker, Nikhil | - |
dc.contributor.nonIdAuthor | Sarkar, Souvarish | - |
dc.contributor.nonIdAuthor | Harischandra, Dilshan S. | - |
dc.contributor.nonIdAuthor | Neal, Matthew | - |
dc.contributor.nonIdAuthor | Jin, Huajun | - |
dc.contributor.nonIdAuthor | Saminathan, Hariharan | - |
dc.contributor.nonIdAuthor | Langley, Monica | - |
dc.contributor.nonIdAuthor | Charli, Adhithiya | - |
dc.contributor.nonIdAuthor | Samidurai, Manikandan | - |
dc.contributor.nonIdAuthor | Rokad, Dharmin | - |
dc.contributor.nonIdAuthor | Ghaisas, Shivani | - |
dc.contributor.nonIdAuthor | Pletnikova, Olga | - |
dc.contributor.nonIdAuthor | Dawson, Valina L. | - |
dc.contributor.nonIdAuthor | Dawson, Ted M. | - |
dc.contributor.nonIdAuthor | Anantharam, Vellareddy | - |
dc.contributor.nonIdAuthor | Kanthasamy, Anumantha G. | - |
dc.contributor.nonIdAuthor | Kanthasamy, Arthi | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | SRC-FAMILY KINASES | - |
dc.subject.keywordPlus | DOPAMINERGIC-NEURONS | - |
dc.subject.keywordPlus | COMPLEX-I | - |
dc.subject.keywordPlus | PARKINSON | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | IL-1-BETA | - |
dc.subject.keywordPlus | BETA | - |
dc.subject.keywordPlus | EXPRESSION | - |
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