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A small protein previously badociated with cell dysfunction and death
in fact, plays a vital role in repairing DNA breaks,
according to new research by Oregon Health & scientists
University of Science.
The discovery, published in the journal Scientific reports, marks the first demonstration of the role that alpha-synuclein plays in preventing the death of neurons in brain diseases such as Parkinson's disease, which affects 1.5 million people in the United States alone.
The results suggest that it would be possible to design new
therapies to replace the function of alpha-synuclein or to improve it in humans
Parkinson's disease and other neurodegenerative disorders.
Aggregates of alpha-synuclein, called Lewy bodies, have long been badociated with Parkinson's disease and other forms of dementia.
The published study sheds new light on this process.
The results suggest that Lewy bodies are problematic because
they extract the alpha-synuclein protein from the nucleus of brain cells. the
study, which examined live mouse cells and the post-mortem brain
tissue in humans, reveals that these proteins perform a crucial function
by repairing the breaks that occur along the vast strands of DNA present in
the nucleus of each cell of 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, leading to the widespread death of neurons.
"It may be the loss of this function that kills this cell," he said.
lead author Vivek Unni, M.D., Ph.D., badociate professor of
neurology at the OHSU School of Medicine.
The researchers discovered that alpha-synuclein protein was rapidly recruited
at the site of DNA damage in mouse neurons. In addition, they
found an increase in double-strand breaks in the DNA of human tissues and mice
in which the protein was agglomerated as a Lewy body in
the cytoplasm surrounding the nucleus of the cell. Taken together, the
the results suggest that alpha-synuclein plays a crucial role in binding
broken DNA strands in the nucleus of the cell.
In other words: if alpha-synuclein are workers in a factory, it is
similar to all the gather for a prolonged coffee break and leaving
machines without supervision.
Unni, who also sees patients at the OHSU Parkinson Center and
Movement Disorders Program, said that he hoped that these results would lead to
the development of methods to deliver alpha-synuclein proteins in the
cell nucleus or design methods to replace its function.
"This is the first time anyone discovered one of his
functions is the repair of DNA, "Unni said." This is essential for cell survival,
and this seems to be a lost function in Parkinson's disease. "
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