(ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease

被引：75

作者：

Kim, T. W. ^{[1
]}

Cho, H. M. ^{[1
]}

Choi, S. Y. ^{[1
]}

Suguira, Y. ^{[2
]}

Hayasaka, T. ^{[2
]}

Setou, M. ^{[2
]}

Koh, H. C. ^{[3
]}

Hwang, E. Mi ^{[4
]}

Park, J. Y. ^{[5
]}

Kang, S. J. ^{[6
]}

Kim, H. S. ^{[1
]}

Kim, H. ^{[1
]}

Sun, W. ^{[1
]}

机构：

[1] Korea Univ, Coll Med, Dept Anat, Program BK21, Seoul 136705, South Korea

[2] Hamamatsu Univ Sch Med, Dept Cell Biol & Anat, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan

[3] Hanyang Univ, Dept Pharmacol, Coll Med, Seoul 133791, South Korea

[4] KIST, Ctr Funct Connect, Seoul 136791, South Korea

[5] Gyeongsang Natl Univ, Dept Physiol, Sch Med, Jinju 660751, South Korea

[6] Sejong Univ, Dept Mol Biol, Seoul 143747, South Korea

来源：

CELL DEATH & DISEASE | 2013年 / 4卷

基金：

新加坡国家研究基金会;

关键词：

PARP-1; ATP; AMPK; 6-OHDA; Parkinson's disease; APOPTOSIS-INDUCING FACTOR; POLYMERASE-1-DEPENDENT CELL-DEATH; POLY(ADP-RIBOSE) POLYMERASE-1; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; ENERGY-METABOLISM; OXIDATIVE STRESS; MITOCHONDRIA; INHIBITION; AUTOPHAGY;

D O I：

10.1038/cddis.2013.447

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Genetic and epidemiologic evidence suggests that cellular energy homeostasis is critically associated with Parkinson's disease (PD) pathogenesis. Here we demonstrated that genetic deletion of Poly (ADP-ribose) polymerase 1 completely blocked 6-hydroxydopamine-induced dopaminergic neurodegeneration and related PD-like symptoms. Hyperactivation of PARP-1 depleted ATP pools in dopaminergic (DA) neurons, thereby activating AMP-activated protein kinase (AMPK). Further, blockade of AMPK activation by viral infection with dominant-negative AMPK strongly inhibited DA neuronal atrophy with moderate suppression of nuclear translocation of apoptosis-inhibiting factor (AIF), whereas overactivation of AMPK conversely strengthened the 6-OHDA-induced DA neuronal degeneration. Collectively, these results suggest that manipulation of PARP-1 and AMPK signaling is an effective therapeutic approach to prevent PD-related DA neurodegeneration.

引用

页码：e919 / e919

页数：10

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