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
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DOI：
10.1016/j.bbrc.2009.11.022
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Jeong, Joo-Won
中科院分区：
文献类型：
--
作者：
Choi, Jae-Sun;Park, Chan;Jeong, Joo-Won
1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱导的神经毒性是研究帕金森病发病机制的最常用的实验模型。在帕金森病(PD)模型中，1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPP+)可引起帕金森病小鼠神经病理缺陷，1-甲基-4-吡啶(MPP+)可诱导细胞死亡。AMP激活的蛋白激酶(AMPK)是能量稳态的关键调节因子。在本研究中，我们证实了MPTP在小鼠体内激活AMPK，在SH-SY5Y细胞中激活MPP+。化合物C对AMPK的抑制可使MPP+诱导的细胞死亡增加。根据这些结果，我们认为AMPK的激活可能阻止神经细胞的死亡，在PD中起到生存因子的作用。(C)2009 Elsevier Inc.保留所有权利
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