A small protein associated with cell dysfunction and death actually serves a critical function in maintaining cell health by repairing breaks in DNA, according to new research led by scientists at Oregon Health & Science University.
The discovery, published recently in the journal Scientific Reports, demonstrates the role of the protein alpha-synuclein in preventing the death of neurons in the brain. Neuron death is a component of brain diseases such as Parkinson’s, which affects 1.5 million people in the United States.
By developing ways to boost the protein’s function in people with Parkinson’s disease, it may be possible to control the disease’s progress. These proteins repair breaks in the vast strands of DNA present in the nucleus of every cell of the body.
Aggregates of the alpha-synuclein protein are known as known as Lewy bodies. They have long been connected to Parkinson’s and other forms of dementia.
The new study suggests that Lewy bodies form by pulling alpha-synuclein protein out of the nucleus of brain cells. Without this protein, cells can no longer repair worn and aging strands of DNA.
Alpha-synuclein’s role in DNA repair may be crucial in preventing cell death. This function may be lost in brain diseases such as Parkinson’s, leading to the widespread death of neurons.
“It may be the loss of that function that’s killing that cell,” said senior author Vivek Unni, M.D., Ph.D., an associate professor of neurology in the OHSU School of Medicine.
The alpha-synuclein protein seems to play a crucial role in binding broken strands of DNA within the cell’s nucleus.
Put another way, if alpha-synuclein are workers in a factory, it’s akin to all of them gathering for an extended coffee break and leaving the machinery unattended.
Unni, who also sees patients in the OHSU Parkinson Center and Movement Disorders Program, said he hopes that these findings lead to the development of methods to deliver alpha-synuclein proteins into the nucleus of cells or designing methods to replace its function.
“This is the first time that anyone has discovered one of its functions is DNA repair,” Unni said. “That’s critical for cell survival, and it appears to be a function that’s lost in Parkinson’s disease.”