Affiliations: [a] Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (U.A.M.-C.S.I.C.), Cantoblanco, Madrid, Spain | [b] Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain | [c] Hospital Psiquiàtric Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, Reus (Tarragona), Spain | [d] Neurology Service, Hospital Universitario Marqués de Valdecilla, Santander, Spain | [e] Neurology Service, Hospital 12 de Octubre, Madrid, Spain | [f] Servicio de Neurología, Hospital Universitario La Paz (UAM), Madrid, Spain
Correspondence:
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Correspondence to: María J. Bullido, Tel.: +34 91 196 4567; Fax: +34 91 196 4420; E-mail: [email protected].
Abstract: Oxidative stress, which plays a critical role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), is intimately linked to aging, the best established risk factor for AD. Studies in neuronal cells subjected to oxidative stress, mimicking such stress in AD brains, are therefore of great interest. PLA2G3 is the most overexpressed gene in a human neuronal model of oxidative stress induced by the free radical-generating xanthine/xanthine oxidase (X-XOD) system, which provokes apoptotic cell death. In this work, we describe that PLA2G3 gene silencing produced a marked inhibition of X-XOD induced cell death, and that PLA2G3 polymorphisms are associated with AD in a Spanish case-control sample. The capacity to respond to oxidative stress may therefore modulate the risk of AD, and PLA2G3 is a potential target to regulate neuronal damage induced by free radicals.
