University of Leicester research team leads new study strengthening therapeutic potential for dietary interventions.
“This study strengthens the therapeutic potential for Vitamin B3/niacin-based dietary interventions in the treatment of Parkinson’s disease” – Dr Miguel Martins, MRC Toxicology Unit, University of Leicester
People with certain forms of early-onset Parkinson’s disease may benefit from boosting the amount of niacin in their diet, according to new research from the University of Leicester.
Niacin, or Vitamin B3, is found in a variety of foods, including nuts and meat.
The team from the MRC Toxicology Unit at the University of Leicester studied fruit flies with a mutation that mimics the human disease.
The results of the study, which is funded by the Medical Research Council, reveal a mechanism for how early-onset Parkinson’s affects the brain, and point to other drugs that may also help this subset of patients.
Dr Miguel Martins, who led the study, explained: “Parkinson’s disease occurs when dopaminergic neurons in a part of the brain called the substantia nigra are lost. This can happen for a variety of reasons, but in some hereditary cases, the main problem is unhealthy mitochondria – the organelles that power the cell.
“Mutations in genes such as PINK1 prevent cells from clearing out the defective powerhouses. When they accumulate, neurons can’t get enough energy and die. The faulty mitochondria also release toxic molecules that damage their genes encoded by DNA.
“Curiously enough, there’s a compound in the body that’s important for both energy generation and DNA repair. It’s called NAD. With all the mitochondrial damage going on, we wondered if in cases of Parkinson’s the molecule ends up in short supply.”
To investigate this, the team fed fruit flies with the mutated PINK1 gene food supplemented with niacin, which is made into NAD inside the body.
With this extra source of NAD, the flies had far fewer faulty mitochondria than their mutant peers on a regular diet.
The vitamin also prevented the flies from losing neurons.
The team of neuroscientists then examined whether stopping DNA repair from depleting NAD would protect the flies with Parkinson’s – and found that genetically switching this function off kept mitochondria healthy and neurons alive, as well as improved the flies’ strength, mobility and lifespan.
Dr Martins added: “The results suggest that in familial Parkinson’s, available NAD is critical for keeping mitochondria in shape and the disease at bay. Drugs that block NAD-consuming DNA repair already exist to treat cancer. Loading up on niacin probably can’t hurt either.
“While neither of these would be cures, they would expand treatment options for Parkinson’s patients with faulty mitochondria.
“This study strengthens the therapeutic potential for Vitamin B3/niacin-based dietary interventions and PARP inhibition in the treatment of Parkinson’s disease.”
Funding: Funding provided by Medical Research Council.
Source: Dr Miguel Martins – University of Leicester
Image Source: NeuroscienceNews.com image is for illustrative purposes only.
Original Research: Full open access research for “Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson’s disease” by Susann Lehmann, Samantha H. Y. Loh, L. Miguel Martins in Biology Open. Published online October 2016 doi:10.1242/bio.022186
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 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.
“Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson’s disease” by Susann Lehmann, Samantha H. Y. Loh, L. Miguel Martins in Biology Open. Published online October 2016 doi:10.1242/bio.022186