Collaborative Research Team is the First to Link Parkinson’s Disease to Red Pigment in the Brain

Two forms of melanin: black/brown eumelanin and red/yellow pheomelanin color our skin and hair.

In the brain, a specific region called substantia nigra is also pigmented, and the brain pigment also contains eumelanin and pheomelanin. This brain region loses its darkness in Parkinson's disease due to loss of neurons and pigment.

In 2017, investigators led by Xiqun Chen, MD, PhD, from the Department of Neurology at Massachusetts General Hospital, discovered that red hair/fair skin and the redhead-related gene, which are associated with melanoma^1,2, may also be involved in Parkinson's disease³.  

In a new paper published in Progress in Neurobiology, the same team, in collaboration with world’s leading melanin teams in Japan and Italy, found that substantia nigra samples provided by donors with Parkinson’s disease have more red/yellow pigment compared to samples from donors with no neurological diseases.

In contrast, black/brown eumelanin content levels were much lower.

These differences were evident even though samples from Parkinson’s patients had significantly reduced levels of melanin overall. Samples from Alzheimer’s patients did not show similar changes.

This study is the first to link Parkinson’s disease to red pigment in the brain, adding to the team’s earlier findings linking the disease to the lighter pigment in hair/skin.

The new paper also showed that the red pigment is toxic to neurons, as it is to skin cells that produce the pigment^1,2. 

“At the present, we do not know if it is just a coincidence, or if brain pigment is part of the body's pigmentation system, regulated by the same signaling pathway,” says Chen, who is also an assistant professor of Neurology at Harvard Medical School. “It is even more intriguing given the fact that Parkinson's disease and melanoma are risk factors for each other.”

The team will next explore why there are elevated levels of red pigment in Parkinson’s disease and what role—if any—it plays in disease progression.

Funding for the study was provided by The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and the Aligning Science Across Parkinson’s (ASAP) initiative.

References  

1. Mitra D, Luo X, Morgan A, Wang J, Hoang MP, Lo J, Guerrero CR, Lennerz JK, Mihm MC, Wargo JA, Robinson KC, Devi SP, Vanover JC, D'Orazio JA, McMahon M, Bosenberg MW, Haigis KM, Haber DA, Wang Y, Fisher DE. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature. 2012 Nov 15;491(7424):449-53.  
2. Roider EM, Fisher DE. Red Hair, Light Skin, and UV-Independent Risk for Melanoma Development in Humans. JAMA Dermatol. 2016 Jul 1;152(7):751-3.  
3. Chen X, Chen H, Cai W, Maguire M, Ya B, Zuo F, Logan R, Li H, Robinson K, Vanderburg CR, Yu Y, Wang Y, Fisher DE, Schwarzschild MA. The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival. Ann Neurol. 2017 Mar;81(3):395-406.  

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.