The discovery could lead to new treatments for Parkinson's disease and other brain diseases

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The discovery could lead to new treatments for Parkinson's disease and other brain diseases

A small protein previously associated with cell dysfunction and death actually plays a critical role in repairing DNA breaks, according to new research by scientists at Oregon Health & Science University.

This discovery, published today in Scientific Reports, marks the first demonstration of the role of alpha-synuclein in preventing neuron death in brain diseases such as Parkinson's disease, which affects 1.5 million people in the United States alone.

The results suggest that it may be possible to design new treatments to replace or increase alpha-synuclein function in people with Parkinson's disease and other neurodegenerative diseases.

Alpha-synuclein aggregates, called Lewy bodies, have long been linked to Parkinson's disease and other forms of dementia.

The study published today sheds new light on this process.

The results suggest that Lewy bodies are problematic because they remove alpha-synuclein protein from the nucleus of brain cells. The study, which examined living mouse cells and post-mortem brain tissue in humans, found that these proteins play a crucial role in repairing ruptures that occur along the large strands of DNA present in the nucleus of each cell in the body.

The role of alpha-synuclein in DNA repair can be crucial in preventing cell death. This function can be lost in brain diseases such as Parkinson's disease, leading to the widespread death of neurons.

"It may be the loss of this function that is killing this cell," said lead author Vivek Unni, MD, PhD, Associate Professor of Neurology at the OHSU School of Medicine.

The researchers found that alpha-synuclein protein was rapidly recruited from the site of DNA damage in mouse neurons. In addition, they found an increase in double-stranded ruptures in the DNA of human tissues and mice, where the protein was agglomerated as a Lewy body in the cytoplasm surrounding the cell nucleus. Together, the results suggest that alpha-synuclein plays a crucial role in binding broken DNA strands in the cell nucleus.

In other words: If the alpha-synuclein is a factory worker, it is as if they all gather for an extended coffee break and leave the machines unattended.

Mr. Unni, who also sees patients from the OHSU Parkinson Centre and the Movement Disorders Program, said he hopes these results will lead to the development of methods to administer alpha-synuclein proteins into the cell nucleus or to the design of methods to replace its function.

"This is the first time anyone has discovered that one of its functions is DNA repair," said Mr. Unni. "This is crucial for cell survival, and it is a function that seems to have disappeared in Parkinson's disease."