A gene variant resulting in red hair and fair skin, already known to increase the risk of melanoma, may also predispose carriers to the development of Parkinson's disease (PD), a recent study conducted in mice has found.
Researchers have found different variants of the MC1R gene, which regulates production of melanin pigment, appear to alter the amount of dopamine-producing cells in the area of the brain affected by Parkinson's disease.
'This study is the first to show direct influences of the melanoma-linked MC1R gene on dopaminergic neurons in the brain and may provide evidence for targeting MC1R as a novel therapeutic strategy for PD,' said lead investigator on the study Dr Xiqun Chen, assistant professor of neurology at Harvard Medical School and Massachusetts General Hospital.
Different variants of MC1R result in different types and distributions of melanin, which in turn influence skin and hair colour in humans and animals. A link between melanoma (skin cancer) and a MC1R variant known to produce fair skin and red hair has been shown in mice and humans. People with Parkinson's disease also have an increased risk of developing melanoma but not other cancers, and the mechanisms underlying this association have not yet been identified.
The study, published in the Annals of Neurology, addressed these associations by investigating the activity of the red-hair variant of MC1R in the substantia nigra: the area of the brain most affected by Parkinson's disease.
The researchers found that under normal circumstances, the MC1R gene was expressed in the dopamine-producing cells of the substantia nigra. However, mice carrying the red-hair variant of MC1R had fewer dopamine-producing cells in this region, and the cells were more sensitive to toxins known to produce Parkinson's symptoms.
Parkinson's disease is a neurodegenerative disorder mainly affecting motor functions, producing symptoms such as tremor, and rigid and slow movements. Other symptoms, such as cognitive problems, dementia and depression, may also occur.
There is no single known cause of Parkinson's disease: a large number of genetic and environmental influences are known to influence the risk of developing the disorder, including exposure to pesticides or previous head trauma. Thus the MC1R variant may only contribute a small effect to the total picture. Recent studies have also questioned the notion of a link between Parkinson's disease and red hair colour.
Dr Chen argued that MC1R activity may prove a protective factor in Parkinson's disease: 'Our findings suggest further investigation into the potential of MC1R-activating agents as novel neuroprotective therapies for PD, and together with epidemiological evidence, may offer information that could guide those carrying MC1R variants to seek advice from dermatologists or neurologists about their personal risk for melanoma and Parkinson's disease'.