Protein linked to Parkinson’s also found to drive melanoma growth

A small protein that is involved in neurodegeneration that leads to Parkinson’s disease also drives a kind of skin cancer that is known as melanoma, new research led by Oregon Health & Science University Finds.

The study, published today in the magazine Science is progressingsuggests new ways for the development of medicines to reduce the risk of development both Parkinson’s and skin cancer by focusing on the alpha synuclein protein, which seems to play a crucial role in regulating cellular functions.

“Developing medicines that focus on Alfa-Synuclein can be useful in both diseases,” said senior author Vivek Unni, MD, Ph.D., a university teacher Neurology at the OHSU School of Medicine.

The finding builds on an earlier discovery of Unni and colleagues published in 2019 and who have established that Alfa Synuclein helps to perform a critical function by restoring double strict fractures in the DNA of brain cells known as neurons. They believe that this function is crucial in preventing cell death, which occurs when Alfa-Synuclein leaves the core of the cell and instead lumps that is known as Lewy-limbles in Parkinson’s and Lewy Body Dementia.

The new study, conducted in melanoma cells and led by OHSU MD/Ph.D. Student Moriah Arnold, Ba, Ph.D., finds the opposite effect with regard to melanoma.

In melanoma, researchers discovered that Alfa Synuclein is doing its job too well – so that cells can prolifiable as cancer.

Skin cells grow and die constantly and are replaced. That’s normal. The problem comes when the cells that have to die do not. “

VIVEK Unni, MD, Ph.D., Assistantial teacher Neurology, OHSU School of Medicine

Researchers discovered that Alfa-Synuclein in melanomas did not seem to leave the core and to aggregate like with neurons in Parkinson’s. The opposite occurs instead. They increase in the core and perform their function too well in the nucleolus of the core of each melanoma cell: identifying double strict breaks in DNA and then recruiting a different type of protein, known as known as 53BP1To repair them.

This can lead to runaway cellular replication – cancer.

Unlike, Unni said, a similar increase in Alfa-Synuclein leads to cellular dead In Parkinson’s. Why? In neurons in contrast to skin cells, an abundance of alpha synuclein seems to pull them out of the core of the cell in clusters forming in the cytoplasm around the core, Unni said. This in turn leads to cellular death.

“A neuron must live the whole life of a person,” said Unni. “When Alfa synuclein reaches a turning point of abundance, it can no longer perform its normal function and the neuron dies.”

The study suggests that it is possible to develop a medicine that lowers the level of Alfa-Synuclein or modulates its function to treat melanoma, he said. As an alternative, he said that his research is now investigating other ways to increase the recruitment of the binding protein 53BP1 To replace the function of Alfa-Synuclein as a possible treatment for that of Parkinson’s.

“This offers a framework for understanding the relationship between (Parkinson’s) and melanoma disease and offers potential therapeutic goals in melanoma that are aimed at reducing Asyn-mediated nucleolar double strict breaking repair,” the authors conclude.