RT Journal Article
T1 The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway.
A1 Bravo San Pedro, José Manuel
A1 González Polo, Rosa A.
AB 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 prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson's disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks 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-aminophenylthio]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 exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells.
PB Springer
SN 1420-682X
YR 2013
FD 2013-01
LK https://hdl.handle.net/20.500.14352/128836
UL https://hdl.handle.net/20.500.14352/128836
LA eng
NO Bravo-San Pedro JM, Niso-Santano M, Gómez-Sánchez R, Pizarro-Estrella E, Aiastui-Pujana A, Gorostidi A, Climent V, López de Maturana R, Sánchez-Pernaute R, López de Munain A, Fuentes JM, González-Polo RA. The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell Mol Life Sci. 2013 Jan;70(1):121-136.
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III (España)
NO Gobierno Vasco
NO Junta de Extremadura
NO Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
NO FUNDESALUD
DS Docta Complutense
RD 24 dic 2025