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- Title
(ADP-ribose) polymerase 1 and AMP-activated protein kinase mediate progressive dopaminergic neuronal degeneration in a mouse model of Parkinson's disease.
- Authors
Kim, T. W.; Cho, H. M.; Choi, S. Y.; Suguira, Y.; Hayasaka, T.; Setou, M.; Koh, H. C.; Hwang, E. Mi; Park, J. Y.; Kang, S. J.; Kim, H. S.; Kim, H.; Sun, W.
- 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.
- Publication
Cell Death & Disease, 2013, Vol 4, Issue 11, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/cddis.2013.447