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Daniel Alvarez-Fischer, Carmen Noelker, Anne Grünewald, Franca Vulinović, Serge Guerreiro, Julia Fuchs, Lixia Lu, Anne Lombès, Etienne C. Hirsch, Wolfgang H. Oertel, Patrick P. Michel and Andreas Hartmann Probenecid potentiates MPTP/MPP+ toxicity by interference with cellular energy metabolism Journal of Neurochemistry 127

Article first published online: 8 JUL 2013 | DOI: 10.1111/jnc.12343

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We showed in the present study that probenecid lowers the intra-cellular ATP production by interfering with the cellular metabolism (black and green arrows). We excluded an altered MPP+ uptake via dopamine transporter (DAT) (blue arrow) or a disturbed glycolysis pathway as cause of the potentiated MPP+ toxicity and showed an indirect reduction in the Complex I activity. We therefore hypothesize (red dotted lines) that probenecid acts either by altering substrate oxidation downstream of pyruvate or by influencing the citric acid cycle. We showed that deleterious effects of probenecid can be reversed by extra-cellular ATP (red arrows).

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