Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/39086
Title: Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease.
Authors: Lehmann, Susann
Loh, Samantha H. Y.
Martins, L. Miguel
First Published: 23-Dec-2016
Publisher: Company of Biologists: OAJ
Citation: Biology Open, 2016
Abstract: Familial forms of Parkinson's disease (PD) caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is essential for both generating energy in mitochondria and nuclear DNA repair through NAD(+)-consuming poly(ADP-ribose) polymerases (PARPs). We found alterations in NAD(+) salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD(+) precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration. Additionally, a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants. We conclude that enhancing the availability of NAD(+) by either the use of a diet supplemented with NAD(+) precursors or the inhibition of NAD(+)-dependent enzymes, such as PARPs, which compete with mitochondria for NAD(+) is a viable approach to preventing neurotoxicity associated with mitochondrial defects.
DOI Link: 10.1242/bio.022186
eISSN: 2046-6390
Links: http://bio.biologists.org/content/early/2016/12/14/bio.022186
http://hdl.handle.net/2381/39086
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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