AMP-activated protein kinase is activated in Parkinson's disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

The selective loss of dopaminergic neurons in the substantia nigra pars compacta is a feature of Parkinson's disease (PD) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity is the most common experimental model used to investigate the pathogenesis of PD Administration of MPTP in mice produces neuropathological defects as observed in PD and 1-methyl-4-pyridinium (MPP+) induces cell death when neuronal cell cultures are used. AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. In the present Study, we demonstrated that AMPK is activated by MPTP in mice and MPP+ in SH-SY5Y cells The inhibition of AMPK by compound C resulted in ail increase in MPP+-induced cell death We further showed that overexpression of AMPK increased cell viability after exposure to MPP+ in SH-SY5Y cells Based on these results, we suggest that activation of AMPK might prevent neuronal cell death and play a role as a survival factor in PD. (c) 2009 Elsevier Inc All rights reserved