08 Apr Disruptive Amyloid Links Melanoma and Parkinson’s Disease
MedicalResearch.com Interview with:
Dexter N. Dean, Ph.D.
Laboratory of Protein Conformation and Dynamics
Biochemistry and Biophysics Center
National Heart, Lung, and Blood Institute
National Institutes of Health
MedicalResearch.com: What is the background for this study? How do α-synuclein and Pmel function in the skin?
Response: Studies have shown that melanoma occurs more frequently in Parkinson’s disease (PD) patients as compared to the general population, and that individuals with melanoma are more susceptible to PD. The amyloid-forming protein alpha-synuclein, traditionally associated with PD, is also found in melanoma cells. The exact function of alpha-synuclein in melanoma cells is unclear, but an inverse correlation exists between the amount of alpha-synuclein and the amount of pigmentation, suggesting that alpha-synuclein disrupts melanin biosynthesis. Pmel is a functional amyloid protein that supports melanin biosynthesis by serving as a scaffold for melanin polymerization.
MedicalResearch.com: What are the main findings?
Response: Using cultured human SK-MEL 28 melanoma cells, two complementary methods were used to show that alpha-synuclein is present in melanosomes, the site of melanin biosynthesis, alongside Pmel. This interaction was further explored using purified alpha-synuclein protein and a purified, amyloid-forming fragment of Pmel called the repeat domain (RPT). It was found that in an aggregated, amyloid state, alpha-synuclein accelerated RPT aggregation to form a fibril structure that it normally doesn’t adopt on its own. And in a non-aggregated state, alpha-synuclein inhibited RPT aggregation altogether.
MedicalResearch.com: What should readers take away from your report?
Response: This work suggests that amyloid interplay between alpha-synuclein and Pmel may be one of the underlying mechanisms as to how alpha-synuclein disrupts melanin biosynthesis in melanoma cells, which could contribute to melanoma progression.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future research interests are to more broadly understanding the function of alpha-synuclein in melanoma cells, which may yield insights into how it acts to promote melanoma cell survival. This may also be applicable in PD research, since both melanocytes and dopaminergic neurons are derived from the same progenitor cells.
Any disclosures? This work was funded by the Intramural Research Program at the National Institutes of Health. I declare no competing financial interests. My thoughts and opinions are my own and do not necessarily represent those of the National Institutes of Health or the National Heart, Lung, and Blood Institute.f
Defining an amyloid link between Parkinson’s disease and melanoma
Abstract presented at 2021 American Chemical Society.
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