CONICET | Buscador de Institutos y Recursos Humanos

M.A. Conde, M.I. Funk, N.P. Alza, R.M. Uranga, G.A. Salvador. Maneb and alpha-synuclein: friends or foes in neuronal toxicity. XXXV Congreso Anual de la Sociedad de Investigación en Neurociencias (SAN), Argentina, 7-9 de octubre de 2020.Maneb and α-synuclein: friends or foes in neuronal toxicity?Conde MA; Funk M; Alza NP; Uranga RM; Salvador GA. Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB). DBByF-UNS.Maneb (Mb) exposure and α-synuclein (α-syn) overexpression are triggering factors of Parkinson?s disease. In this work, we studied the response to Mb toxicity in neurons stably expressing the human wild type α-syn gene (WT α-syn).In control neurons, Mb cytotoxicity involved the increase in reactive oxygen species (ROS), α-syn overxpression and the loss in plasma membrane integrity. Experiments with the antioxidant N-acetyl cysteine proved that the increase in α-syn expression induced by the pesticide was redox-dependent. Accordingly, WT α-syn neurons exposed to Mb showed decreased ROS content and less plasma membrane damage , with no additional changes in α-syn expression. To further characterize the response to Mb exposure, FoxO3a and Nrf2, two transcription factors activated upon cell injury, were evaluated. Mb exposure triggered Akt phosphorylation and the kinase-dependent FoxO3a inhibition in control cells. However, Mb exposure had no differential effect on FoxO3a status in WT α-syn cells. On the other hand, the expression of Nrf2-regulated phase-two antioxidant genes was increased in WT α-syn neurons. These results show that a neuroprotective response can be elicited when α-syn is overexpressed prior to pesticide exposure. Additional studies are necessary to solve the question whether α-syn is friend or foe in pesticide-induced toxicity.

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