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 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.
Choi
Jae-Sun
JS
Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Park
Chan
C
Jeong
Joo-Won
JW
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D015259:Dopamine Agents / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010300:Parkinson Disease / Q000201:enzymology*
D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D055372:AMP-Activated Protein Kinases