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

T. W. Kim, H. M. Cho, S. Y. Choi, Y. Suguira, T. Hayasaka, M. Setou, H. C. Koh, E. Mi Hwang, J. Y. Park, S. J. Kang, H. S. Kim, H. Kim, W. Sun

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere919
JournalCell Death and Disease
Volume4
Issue number11
DOIs
Publication statusPublished - 2013 Nov

Keywords

  • 6-OHDA
  • AMPK
  • ATP
  • PARP-1
  • Parkinson's disease

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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