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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-11

AUTHORS

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

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. More... »

PAGES

e919

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cddis.2013.447

DOI

http://dx.doi.org/10.1038/cddis.2013.447

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027453155

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24232095


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