Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease
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 i...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2017-02-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/6/2/141 |
| _version_ | 1818734476529762304 |
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| author | Susann Lehmann Samantha H. Y. Loh L. Miguel Martins |
| author_facet | Susann Lehmann Samantha H. Y. Loh L. Miguel Martins |
| author_sort | Susann Lehmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T00:05:58Z |
| format | Article |
| id | doaj.art-1c960172f36143cd88c4433ed902d0ae |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-18T00:05:58Z |
| publishDate | 2017-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-1c960172f36143cd88c4433ed902d0ae2022-12-21T21:27:48ZengThe Company of BiologistsBiology Open2046-63902017-02-016214114710.1242/bio.022186022186Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's diseaseSusann Lehmann0Samantha H. Y. Loh1L. Miguel Martins2 MRC Toxicology Unit, Lancaster Road, Leicester LE1 9HN, UK MRC Toxicology Unit, Lancaster Road, Leicester LE1 9HN, UK MRC Toxicology Unit, Lancaster Road, Leicester LE1 9HN, UK 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.http://bio.biologists.org/content/6/2/141DrosophilaMitochondriaNAD+NAMNiacinNucleotide metabolismParkinson's diseasePARPPINK1 |
| spellingShingle | Susann Lehmann Samantha H. Y. Loh L. Miguel Martins Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease Biology Open Drosophila Mitochondria NAD+ NAM Niacin Nucleotide metabolism Parkinson's disease PARP PINK1 |
| title | Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease |
| title_full | Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease |
| title_fullStr | Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease |
| title_full_unstemmed | Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease |
| title_short | Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease |
| title_sort | enhancing nad salvage metabolism is neuroprotective in a pink1 model of parkinson s disease |
| topic | Drosophila Mitochondria NAD+ NAM Niacin Nucleotide metabolism Parkinson's disease PARP PINK1 |
| url | http://bio.biologists.org/content/6/2/141 |
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