“Red Hair” Gene Variant May Underlie Association Between Melanoma & Parkinson’s Disease

A gene variant that produces red hair and fair skin in humans and in mice, and which increases the risk of the dangerous skin cancer melanoma, may also contribute to the known association between melanoma and Parkinson's disease. In a paper appearing in the March 2017 issue of Annals of Neurology and previously published online (January 23, 2017), Massachusetts General Hospital (MGH) investigators report that mice carrying the red-hair variant of the melanocortin 1 receptor (MC1R) gene have reduced production of the neurotransmitter dopamine in the substantia nigra [the brain structure in which dopamine-producing neurons are destroyed in Parkinson's disease (PD)] and are more susceptible to toxins known to damage those neurons. "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," says Xiqun Chen, M.D., Ph.D., of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), lead and corresponding author of the report. "It also forms a foundation for further interdisciplinary investigations into the dual role of this gene in tumorigenesis within melanocytes (the pigment cells in which melanoma develops) and the degeneration of dopaminergic neurons, improving our understanding of why and how melanoma and Parkinson's disease are linked." Inherited variants of the MC1R gene determine skin pigmentation, with the most common form leading to greater production of the darker pigment called eumelanin and the red-hair-associated variant, which inactivates the gene's function, increasing production of the lighter pigment called pheomelanin.
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