RT Journal Article
T1 G2019S LRRK2 mutant fibroblasts from Parkinson's disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy
A1 Yakhine-Diop, Sokhna M S
A1 Bravo San Pedro, José Manuel
A1 Gómez Sánchez, Ruben
A1 Pizarro Estrella, Elisa
A1 Rodríguez Arribas, Mario
A1 Climent, Vicente
A1 Aiastui, Ana
A1 López de Munain, Adolfo
A1 Fuentes, José M.
A1 González Polo, Rosa A.
AB Parkinson's disease (PD) is a neurodegenerative disorder of unknown etiology. It is considered as a multifactorial disease dependent on environmental and genetic factors. Deregulation in cell degradation has been related with a significant increase in cell damage, becoming a target for studies on the PD etiology. In the present study, we have characterized the parkinsonian toxin 1-methyl-4-phenylpyridinium ion (MPP(+))-induced damage in fibroblasts from Parkinson's patients with the mutation G2019S in leucine-rich repeat kinase 2 protein (LRRK2) and control individuals without this mutation. The results reveal that MPP(+) induces mTOR-dependent autophagy in fibroblasts. Moreover, the effects of caspase-dependent cell death to MPP(+) were higher in cells with the G2019S LRRK2 mutation, which showed basal levels of autophagy due to the G2019S LRRK2 mutation (mTOR-independent). The inhibition of autophagy by 3-methyladenine (3-MA) treatment reduces these sensitivity differences between both cell types, however, the inhibition of autophagosome-lysosome fusion by bafilomycin A1 (Baf A1) increases these differences. This data confirm the importance of the combination of genetic and environmental factors in the PD etiology. Thereby, the sensitivity to the same damage may be different in function of a genetic predisposition, reason why individuals with certain mutations can develop some early-onset diseases, such as individuals with G2019S LRRK2 mutation and PD.
PB Elsevier
SN 0300-483X
YR 2014
FD 2014-10
LK https://hdl.handle.net/20.500.14352/128972
UL https://hdl.handle.net/20.500.14352/128972
LA eng
NO Yakhine-Diop SMS, Bravo-San Pedro JM, Gómez-Sánchez R, Pizarro-Estrella E, Rodríguez-Arribas M, Climent V, Aiastui A, López de Munain A, Fuentes JM, González-Polo RA. G2019S LRRK2 mutant fibroblasts from Parkinson's disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy. Toxicology. 2014 Jul 10;324:1–9.
NO Instituto de Salud Carlos III (España)
NO Ministerio de Economia y Competitividad (España)
NO Instituto Biodonostia
DS Docta Complutense
RD 25 feb 2026