Maneb and alpha-synuclein: friends or foes in neuronal toxicity

CONDE, MELISA A.; FUNK, MELANIA I.; ALZA, NATALIA P.; URANGA, ROMINA M.; SALVADOR, GABRIELA A.

Congreso; XXXV Congreso Anual de la Sociedad de Investigación en Neurociencias (SAN); 2020

SAN

Maneb (Mb) exposure and alpha-synuclein (a-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 a-syn gene (WT a-syn).In control neurons, Mb cytotoxicity involved an increase in reactive oxygen species (ROS), a-syn overxpression and the loss in plasma membrane integrity. Experiments with the antioxidant N-acetylcysteine proved that the increase in a-syn expression induced by the pesticide was redox-dependent. In addition, WT a-syn neurons exposed to Mb showed decreased ROS content and less plasma membrane damage, with no additional changes in a-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 a-syn cells. On the other hand, the expression of Nrf2-regulated phase-two antioxidant genes was increased in WT a-syn neurons. These results show that a neuroprotective response can be elicited when a-syn is overexpressed prior to pesticide exposure. Additional studies are necessary to solve the question whether a-syn is friend or foe in pesticide-induced toxicity.