Ginger Gene Uncovers Link Between Parkinson’s Disease & Melanoma
A genetic variant responsible for red hair and fair skin in humans and mice may also be involved in the link between Parkinson’s Disease (PD) and the skin cancer melanoma, according to new research. The study, published in Annals of Neurology, reveals a link between the red-hair variant of the Melanocortin 1 Receptor (MC1R) gene and reduced production of dopamine in the substantia nigra in mice, as well as an increased susceptibility to known toxins in the same neurons. The substantia nigra is a region of the brain that is heavily affected by PD, when dopamine-producing neurons are destroyed by the condition.
This is the second time this month that our understanding of PD has been expanded.
For many years, researchers have theorised about the genomic links between PD and melanoma, and now a team from Massachusetts General Hospital believe that they may have found a solution in a ‘ginger gene.’
“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 Xiqun Chen, M.D., Ph.D., lead investigator of the study, Assistant Professor of Neurology at Harvard Medical School, and Assistant in Neuroscience at the MassGeneral Institute for Neurodegenerative Disease. “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.”
Previous studies have noted that patients with PD display a lower risk of developing most types of cancer, with the exception of melanoma, where the risk is disproportionately high when compared to people without PD. The reverse is also true; patients with melanoma have a higher risk of developing PD.
Other investigations into melanoma have also centred on MC1R, which helps to determine skin pigmentation. The most common variant of the gene promotes production of eumelanin, a dark pigment, whereas the red-hair associated variant inactivates the gene and thereby promotes pheomelanin production. Pheomelanin is a much lighter pigment that offers less protection from UV rays, which can cause melanoma, but may also directly contribute to development of the disease according to prior studies.
Using this previous work, the team from MGH investigated the role MC1R plays in PD and more specifically within the dopamine-producing neurons in the substantia nigra. They were able to show that mice with the common form of the gene expressed it within the neurons, whereas red-haired mice with an inactivated gene had fewer dopamine-producing neurons and displayed a progressive decline in movement and dopamine levels as they aged. The team also found indications of oxidative stress damage on adjacent neurons, something that previous work has implied to be linked to pheomelanin-associated melanoma risk.
“Since MC1R regulates pigmentation and red hair is a shared risk factor for both melanoma and PD, it is possible that, in both conditions, MC1R’s role involves pigmentation and related oxidative stress,” Dr. Chen said. “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 PD.”