Publication

G2019S Mutation of LRRK2 Increases Autophagy via MEK/ERK Pathway

Yakhine-Diop, S. M. S., Rodríguez-Arribas, M., Gómez-Sánchez, R., Pizarro-Estrella, E., Niso-Santano, M., González-Polo, R. A., Bravo-San Pedro, J. M. & Fuentes, J. M., 2016, Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging. Elsevier, Vol. 9. p. 123-142 20 p. (Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

  • Sokhna M.S. Yakhine-Diop
  • Mario Rodríguez-Arribas
  • Rubén Gómez-Sánchez
  • Elisa Pizarro-Estrella
  • Mireia Niso-Santano
  • Rosa A. González-Polo
  • José M. Bravo-San Pedro
  • José M. Fuentes
Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by mitochondrial dysfunction, oxidative stress, and later neuronal death. Several genetics and environmental factors have been implicated in the {PD} pathogenesis. 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. The deregulation of autophagic process in nerve cells is thought to be a possible cause of PD. {G2019S} mutant fibroblasts exhibited higher autophagic activity that can trigger cell death. In this sense, {G2019S} mutant cells displayed increased apoptosis hallmarks and enough susceptibility to MPP+ (1-methyl-4-phenylpyridinium). {G2019S} {LRRK2} heightens the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126) reduced the enhanced autophagy suggesting that the {G2019S} mutation induces autophagy via MEK/ERK pathway. Further, the inhibition of this exacerbated autophagy reduces the sensitivity remarked in {G2019S} mutant cells.
Original languageEnglish
Title of host publicationAutophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging
PublisherElsevier
Chapter5
Pages123-142
Number of pages20
Volume9
ISBN (Print)978-0-12-802936-7
Publication statusPublished - 2016

Publication series

NameAutophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

ID: 59979452