Red Hair Gene May Increase Risk of Parkinson's Disease

New findings suggest a genetic variant that causes red hair and fair skin may increase the risk of melanoma and Parkinson’s disease in humans and animals.

The authors of study a published by the Annals of Neurology found that mice models with the melanocortin 1 receptor (MC1R) gene variant that causes red hair have reduced production of the dopamine neurotransmitters in the substantia nigra, which is the part of the brain is where neurons are destroyed in Parkinson’s disease. This may leave neurons more susceptible to harm from toxins.

"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 and corresponding author Xiqun Chen, MD, PhD. “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."

Variants of the MC1R gene are responsible for various skin pigmentations. The most common variant creates darker pigment (eumelanin), while a less common variant causes the production of a lighter pigment (pheomelanin).

Pheomelanin is known to provide less protection against the sun than eumelanin, and previous studies also show that it may increase the risk of melanoma. This explains why individuals with light hair and eyes are more susceptible to sunburn and skin cancers.

Although patients with Parkinson’s disease generally have a reduced risk of cancer, they have an increased risk of developing melanoma, and vice versa, according to the study. Other studies have linked Parkinson’s disease with the MC1R variant that produces red hair.

In the current study, the authors aimed to determine the role of the red hair variant in Parkinson’s disease, especially in the dopamine-producing neurons of the substantia nigra.

The authors discovered that the more common MC1R variant was expressed in the dopamine-producing neurons in the substantia nigra. However, in red-haired mice, the gene was inactive. These mice were observed to have less dopamine-producing neurons, decreased movement, and low dopamine levels as they aged, according to the study.

Mice with the rare variant were also observed to be more susceptible to damage from toxic substances known to damage dopamine-producing neurons, and had increased levels of oxidative stress, which has been linked to melanoma risk, according to the study.

The authors discovered that treating mice with a substance to amplify MC1R signaling effectively reduced sensitivity to neurotoxins among animals with the more common variant. This finding demonstrates a potentially protective role for MC1R.

"Since MC1R regulates pigmentation and red hair is a shared risk factor for both melanoma and Parkinson's disease, it is possible that, in both conditions, MC1R's role involves pigmentation and related oxidative stress," Dr Chen concluded. "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."