A new study explored the mechanism of how a genetic variant that leads to red hair and fair skin, and increases the risk of melanoma among people with these traits, may also play a role in Parkinson’s disease (PD). The research was published in the January 21 online edition of Annals of Neurology.
Scientists have long known that people with PD have an increased risk of melanoma, a dangerous skin cancer. The reverse is also true too: people who have melanoma have a higher risk of developing PD. Researchers led by Xiqun Chen, M.D., Ph.D., at Massachusetts General Hospital in Boston, set out to find a biological basis for these connections.
The scientists focused on a gene called melanocortin 1 receptor (MC1R), which regulates skin pigment. In people, when a mutation turns the gene “off,” it is linked to red hair and fair skin.
In mice, scientists studied the brain cells typically impacted by Parkinson’s. They compared brain cells from mice with a common “on” form of MC1R with the brain cells of mice with the “off” version similar to the one for red hair/fair skin in humans. They first studied whether the gene affected brain cells. Then they exposed brain cells to toxins known to produce PD-like damage in the brain. Finally, they tested the effects of boosting the activity of the MC1R.
- Mice with the gene variant for red hair produced less dopamine in their brains, leading to movement symptoms similar to PD.
- In mice with the gene variant for red hair, the brain area affected by PD was more susceptible to toxins known to damage dopamine neurons.
- Boosting the gene’s activity protected neurons against these toxins.
What Does It Mean?
Variations in the MC1R gene are linked to red hair and fair skin. Whether these variants are associated with PD is controversial.
In this study, scientists aimed to investigate the role of the MC1R gene in dopamine neurons. The new discovery of this study is that the activity of the MC1R gene may protect dopamine neurons from damage in PD. This suggests that therapies to boost MC1R activity could potentially protect brain cells in PD. Although this research lies in the future, drugs targeting MC1R are already being investigated to treat certain skin pigment disorders.
The study also emphasizes how population studies — which were used to identify the link between melanoma and PD — provide important clues to help us make new discoveries and find new therapies.
Chen X, Chen H, Cai W, et al. (2017). The Melanoma-Linked “Redhead” MC1R Influences Dopaminergic Neuron Survival. Annals of Neurology DOI: 10.1002/ana.24852 (http://dx.doi.org/10.1002/ana.24852).