Please use this identifier to cite or link to this item:
|Title:||Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson's disease|
Costa, A. C.
Loh, S. H.
Martins, L. Miguel
|Publisher:||Nature Publishing Group for Associazione Differenziamento e Morte Cellulare|
|Citation:||Cell Death and Disease, 2016, 7, e2166|
|Abstract:||The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is an essential co-factor for cellular energy generation in mitochondria as well as for DNA repair mechanisms in the cell nucleus involving NAD(+)-consuming poly (ADP-ribose) polymerases (PARPs). Mitochondrial function is compromised in animal models of Parkinson's disease (PD) associated with PARKIN mutations. Here, we uncovered alterations in NAD(+) salvage metabolism in Drosophila parkin mutants. We show that a dietary supplementation with the NAD(+) precursor nicotinamide rescues mitochondrial function and is neuroprotective. Further, by mutating Parp in parkin mutants, we show that this increases levels of NAD(+) and its salvage metabolites. This also rescues mitochondrial function and suppresses dopaminergic neurodegeneration. We conclude that strategies to enhance NAD(+) levels by administration of dietary precursors or the inhibition of NAD(+)-dependent enzymes, such as PARP, that compete with mitochondria for NAD(+) could be used to delay neuronal death associated with mitochondrial dysfunction.|
|Rights:||Copyright © the authors, 2016. Cell Death and Disease is an open-access journal published by Nature Publishing Group . This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article ’ s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/|
|Appears in Collections:||Published Articles, Dept. of Molecular and Cell Biology|
Files in This Item:
|cddis201672a.pdf||Published (publisher PDF)||796.15 kB||Adobe PDF||View/Open|
Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.