(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, Il Hwan Kim, W. Sun

Research output: Contribution to journalArticle

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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 (US)
Article numbere919
JournalCell Death and Disease
Volume4
Issue number11
DOIs
StatePublished - Nov 1 2013

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Adenosine Diphosphate Ribose
AMP-Activated Protein Kinases
Parkinson Disease
Oxidopamine
Dopaminergic Neurons
Virus Diseases
Atrophy
Homeostasis
Adenosine Triphosphate
Apoptosis

All Science Journal Classification (ASJC) codes

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

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(ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease. / Kim, T. W.; Cho, H. M.; Choi, S. Y.; Suguira, Y.; Hayasaka, T.; Setou, M.; Koh, H. C.; Mi Hwang, E.; Park, J. Y.; Kang, S. J.; Kim, H. S.; Kim, Il Hwan; Sun, W.

In: Cell Death and Disease, Vol. 4, No. 11, e919, 01.11.2013.

Research output: Contribution to journalArticle

Kim, TW, Cho, HM, Choi, SY, Suguira, Y, Hayasaka, T, Setou, M, Koh, HC, Mi Hwang, E, Park, JY, Kang, SJ, Kim, HS, Kim, IH & Sun, W 2013, '(ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease', Cell Death and Disease, vol. 4, no. 11, e919. https://doi.org/10.1038/cddis.2013.447
Kim, T. W. ; Cho, H. M. ; Choi, S. Y. ; Suguira, Y. ; Hayasaka, T. ; Setou, M. ; Koh, H. C. ; Mi Hwang, E. ; Park, J. Y. ; Kang, S. J. ; Kim, H. S. ; Kim, Il Hwan ; Sun, W. / (ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease. In: Cell Death and Disease. 2013 ; Vol. 4, No. 11.
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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.",
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AB - 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.

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