FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2992154881> ?p ?o ?g. }

• W2992154881 endingPage "132" @default.
• W2992154881 startingPage "127" @default.
• W2992154881 abstract "Neurodegeneration in patients with Parkinson’s disease is correlated with the occurrence of Lewy bodies—intracellular inclusions that contain aggregates of the intrinsically disordered protein α-synuclein1. The aggregation propensity of α-synuclein in cells is modulated by specific factors that include post-translational modifications2,3, Abelson-kinase-mediated phosphorylation4,5 and interactions with intracellular machineries such as molecular chaperones, although the underlying mechanisms are unclear6–8. Here we systematically characterize the interaction of molecular chaperones with α-synuclein in vitro as well as in cells at the atomic level. We find that six highly divergent molecular chaperones commonly recognize a canonical motif in α-synuclein, consisting of the N terminus and a segment around Tyr39, and hinder the aggregation of α-synuclein. NMR experiments9 in cells show that the same transient interaction pattern is preserved inside living mammalian cells. Specific inhibition of the interactions between α-synuclein and the chaperone HSC70 and members of the HSP90 family, including HSP90β, results in transient membrane binding and triggers a remarkable re-localization of α-synuclein to the mitochondria and concomitant formation of aggregates. Phosphorylation of α-synuclein at Tyr39 directly impairs the interaction of α-synuclein with chaperones, thus providing a functional explanation for the role of Abelson kinase in Parkinson’s disease. Our results establish a master regulatory mechanism of α-synuclein function and aggregation in mammalian cells, extending the functional repertoire of molecular chaperones and highlighting new perspectives for therapeutic interventions for Parkinson’s disease. Chaperones interact with a canonical motif in α-synuclein, which can be prevented by phosphorylation of α-synuclein at Tyr39, whereas inhibition of this interaction leads to the localization of α-synuclein to the mitochondria and aggregate formation." @default.
• W2992154881 created "2019-12-13" @default.
• W2992154881 creator A5005003317 @default.
• W2992154881 creator A5017281155 @default.
• W2992154881 creator A5022733517 @default.
• W2992154881 creator A5025927736 @default.
• W2992154881 creator A5031916238 @default.
• W2992154881 creator A5035221738 @default.
• W2992154881 creator A5046473474 @default.
• W2992154881 creator A5060213327 @default.
• W2992154881 creator A5062457720 @default.
• W2992154881 creator A5062473197 @default.
• W2992154881 creator A5064488209 @default.
• W2992154881 creator A5078715883 @default.
• W2992154881 creator A5082426081 @default.
• W2992154881 creator A5084176856 @default.
• W2992154881 creator A5087874713 @default.
• W2992154881 date "2019-12-04" @default.
• W2992154881 modified "2023-10-06" @default.
• W2992154881 title "Regulation of α-synuclein by chaperones in mammalian cells" @default.
• W2992154881 cites W1971784630 @default.
• W2992154881 cites W1972726656 @default.
• W2992154881 cites W1979591162 @default.
• W2992154881 cites W1980858544 @default.
• W2992154881 cites W1984501109 @default.
• W2992154881 cites W1984678540 @default.
• W2992154881 cites W1992513829 @default.
• W2992154881 cites W1993050837 @default.
• W2992154881 cites W1995520063 @default.
• W2992154881 cites W1997718936 @default.
• W2992154881 cites W2009842820 @default.
• W2992154881 cites W2044627978 @default.
• W2992154881 cites W2054868321 @default.
• W2992154881 cites W2059577301 @default.
• W2992154881 cites W2083440806 @default.
• W2992154881 cites W2086628547 @default.
• W2992154881 cites W2089522371 @default.
• W2992154881 cites W2098276301 @default.
• W2992154881 cites W2116645442 @default.
• W2992154881 cites W2117376526 @default.
• W2992154881 cites W2136956472 @default.
• W2992154881 cites W2138070282 @default.
• W2992154881 cites W2140197221 @default.
• W2992154881 cites W2150148922 @default.
• W2992154881 cites W2167512640 @default.
• W2992154881 cites W2253387945 @default.
• W2992154881 cites W2253997490 @default.
• W2992154881 cites W2335096951 @default.
• W2992154881 cites W2470879573 @default.
• W2992154881 cites W2513782408 @default.
• W2992154881 cites W2553058372 @default.
• W2992154881 cites W2606824156 @default.
• W2992154881 cites W2775514330 @default.
• W2992154881 cites W2794699203 @default.
• W2992154881 cites W2796389302 @default.
• W2992154881 cites W2906543169 @default.
• W2992154881 cites W2953014442 @default.
• W2992154881 doi "https://doi.org/10.1038/s41586-019-1808-9" @default.
• W2992154881 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6930850" @default.
• W2992154881 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31802003" @default.
• W2992154881 hasPublicationYear "2019" @default.
• W2992154881 type Work @default.
• W2992154881 sameAs 2992154881 @default.
• W2992154881 citedByCount "164" @default.
• W2992154881 countsByYear W29921548812020 @default.
• W2992154881 countsByYear W29921548812021 @default.
• W2992154881 countsByYear W29921548812022 @default.
• W2992154881 countsByYear W29921548812023 @default.
• W2992154881 crossrefType "journal-article" @default.
• W2992154881 hasAuthorship W2992154881A5005003317 @default.
• W2992154881 hasAuthorship W2992154881A5017281155 @default.
• W2992154881 hasAuthorship W2992154881A5022733517 @default.
• W2992154881 hasAuthorship W2992154881A5025927736 @default.
• W2992154881 hasAuthorship W2992154881A5031916238 @default.
• W2992154881 hasAuthorship W2992154881A5035221738 @default.
• W2992154881 hasAuthorship W2992154881A5046473474 @default.
• W2992154881 hasAuthorship W2992154881A5060213327 @default.
• W2992154881 hasAuthorship W2992154881A5062457720 @default.
• W2992154881 hasAuthorship W2992154881A5062473197 @default.
• W2992154881 hasAuthorship W2992154881A5064488209 @default.
• W2992154881 hasAuthorship W2992154881A5078715883 @default.
• W2992154881 hasAuthorship W2992154881A5082426081 @default.
• W2992154881 hasAuthorship W2992154881A5084176856 @default.
• W2992154881 hasAuthorship W2992154881A5087874713 @default.
• W2992154881 hasBestOaLocation W29921548812 @default.
• W2992154881 hasConcept C104317684 @default.
• W2992154881 hasConcept C11960822 @default.
• W2992154881 hasConcept C136238340 @default.
• W2992154881 hasConcept C141109615 @default.
• W2992154881 hasConcept C142724271 @default.
• W2992154881 hasConcept C185592680 @default.
• W2992154881 hasConcept C205260736 @default.
• W2992154881 hasConcept C2775932338 @default.
• W2992154881 hasConcept C2775962898 @default.
• W2992154881 hasConcept C2776925932 @default.
• W2992154881 hasConcept C2777916540 @default.
• W2992154881 hasConcept C2779134260 @default.
• W2992154881 hasConcept C2779734285 @default.

• next