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• W3145815418 abstract "Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most pre- valent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkin- son's disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of auto- phagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hall- marks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenyl- thio)butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exac- erbated autophagy reduces the sensitivity observed in G2019S mutant cells. J. M. Fuentes and R. A. Gonzalez-Polo contributed equally to this paper." @default.
• W3145815418 created "2021-04-13" @default.
• W3145815418 creator A5064522694 @default.
• W3145815418 date "2013-01-01" @default.
• W3145815418 modified "2023-09-27" @default.
• W3145815418 title "The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway" @default.
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