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 language | English |
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Article number | e919 |
Journal | Cell Death and Disease |
Volume | 4 |
Issue number | 11 |
DOIs | |
Publication status | Published - 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