Redheads at higher risk of Parkinson's and melanoma

It’s no secret that people with ginger hair and pale skin are more at risk of damage from ultraviolet light, but as it turns out, that’s not the only thing our redheaded brothers and sisters need to be wary of.

Inherited variants of the melanocortin 1 receptor (MC1R) gene determine skin pigmentation. The most common form leads to greater production of the darker pigment, called eumelanin, while the red-hair-associated variant, which inactivates the gene’s function, increases production of the lighter pigment called pheomelanin.

It has already been firmly established that pheomelanin provides less protection from ultraviolet damage to the skin than eumelanin, which is why redheaded people are quicker to burn than others. However, a 2012 study led by Dr David Fisher, from Massachusetts General Hospital (MGH), found that this pigment may also directly contribute to melanoma development.

Examining red and albino redhead mice, Dr Fisher and his colleagues discovered elevated levels of a type of DNA damage typically produced by reactive oxygen species (ROS) — unstable oxygen-containing molecules that can damage cells — in the skin of red mice but not in albino redheads. This supports oxidative damage as the mechanism behind red-pigment-associated melanoma formation, and suggests that antioxidant treatments may be able to reduce this risk.

So what does this have to do with Parkinson’s disease (PD)? Well, it turns out that patients suffering from the degenerative disorder have a reduced risk of developing most types of cancer but a higher-than-expected risk of melanoma. Melanoma patients, meanwhile, have an increased risk of developing PD. Several studies have also found evidence suggesting increased PD risk in individuals with red-hair-associated variants of MC1R.

In a new study, published in the journal Annals of Neurology, Dr Fisher and his colleagues found that in mice with the common form of MC1R, the gene is expressed in dopamine-producing neurons in the substantia nigra — the brain structure in which these neurons are destroyed in PD. The red-haired mice in which the gene was inactivated were found to have fewer dopamine-producing neurons and, as they aged, developed a progressive decline in movement and a drop in dopamine levels.

The mice also were more sensitive to toxic substances known to damage dopamine-producing neurons and had indications of increased oxidative stress — which the 2012 study implied was involved in pheomelanin-associated melanoma risk — in brain structures adjacent to the substantia nigra. Treatment with a substance that increases MC1R signalling reduced the susceptibility of mice with the common variant to a neurotoxin, further supporting a protective role for the gene’s activity.

“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,” said Dr Xiqun Chen from MGH, lead author of the report. “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.”

Image courtesy of Kate Geraets under CC BY-NC 2.0