AMP-activated protein kinase is activated in Parkinson’s disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AMP-activated protein kinase is activated in Parkinson's disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Biochem Biophys Res Commun. 2009 Nov 7;
Authors: Choi JS, Park C, Jeong JW
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 an 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.
PMID: 19903456 [PubMed - as supplied by publisher]
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