Portland, April 2025 — A small protein called alpha-synuclein, long known for its role in Parkinson’s disease, also plays a major part in the development of melanoma, a type of skin cancer, according to new research from Oregon Health & Science University (OHSU). The findings were published in the journal Science Advances.
The study reveals how the same protein behaves very differently in brain and skin cells, potentially opening new paths for drug development targeting both diseases.
“Drugs that target alpha-synuclein could be useful for treating both conditions,” said lead researcher Dr. Vivek Unni, associate professor of neurology at the OHSU School of Medicine.
A Protein with Dual Roles
Alpha-synuclein has already been linked to Parkinson’s disease, where it is known to help repair damaged DNA in brain cells, known as neurons. But when too much of the protein leaves the cell nucleus and forms clumps—called Lewy bodies—it leads to cell death. This is a key feature of both Parkinson’s and Lewy body dementia.
In contrast, the new study found that alpha-synuclein behaves in the opposite way in melanoma cells. Instead of leaving the nucleus, the protein builds up inside it. There, it continues repairing DNA too efficiently, which keeps damaged skin cells alive and causes them to multiply uncontrollably—a hallmark of cancer.
“Skin cells are supposed to grow, die, and be replaced. That’s normal,” Dr. Unni explained. “But when cells that should die survive, cancer can form.”
How the Protein Works
In healthy cells, alpha-synuclein helps fix breaks in DNA by attracting another protein called 53BP1 to the damage site. In neurons, too much alpha-synuclein causes the protein to clump outside the nucleus, which disrupts its normal function and leads to cell death. But in melanoma cells, alpha-synuclein stays in the nucleus and keeps fixing DNA—even when it shouldn’t.
This allows melanoma cells to continue dividing and growing, creating cancer.
“A neuron needs to last a lifetime,” said Dr. Unni. “If alpha-synuclein becomes too abundant, it stops doing its job correctly and the neuron dies. But in melanoma, it does the job too well.”
Hope for New Treatments
The researchers believe that lowering the levels of alpha-synuclein—or adjusting how it functions—could help treat melanoma. For Parkinson’s disease, they are also exploring ways to mimic its DNA-repair role by boosting 53BP1, the protein it recruits.
“This research helps explain the connection between Parkinson’s disease and melanoma,” the authors wrote. “It also points to new targets for therapy focused on how alpha-synuclein repairs DNA in the cell nucleus.”
The study was led by OHSU M.D./Ph.D. student Moriah Arnold and builds on earlier research by Dr. Unni’s team. Their ongoing work continues to explore how one protein can contribute to both cancer and neurodegeneration—and how it might be controlled to help treat both.
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