| Title |
Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson’s disease
|
|---|---|
| Published in |
Cell Death & Disease, March 2016
|
| DOI | 10.1038/cddis.2016.72 |
| Pubmed ID | |
| Authors |
S Lehmann, A C Costa, I Celardo, S H Y Loh, L M Martins |
| 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. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 50% |
| United States | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 50% |
| Members of the public | 2 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 94 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 94 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 16 | 17% |
| Researcher | 15 | 16% |
| Student > Bachelor | 12 | 13% |
| Student > Master | 8 | 9% |
| Student > Postgraduate | 5 | 5% |
| Other | 10 | 11% |
| Unknown | 28 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 17 | 18% |
| Agricultural and Biological Sciences | 16 | 17% |
| Neuroscience | 10 | 11% |
| Medicine and Dentistry | 10 | 11% |
| Chemistry | 4 | 4% |
| Other | 7 | 7% |
| Unknown | 30 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 19. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 December 2016.
All research outputs
#1,738,367
of 23,577,654 outputs
Outputs from Cell Death & Disease
#198
of 6,698 outputs
Outputs of similar age
#30,230
of 302,580 outputs
Outputs of similar age from Cell Death & Disease
#4
of 97 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 6,698 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one has done particularly well, scoring higher than 96% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 302,580 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 97 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.