A team of neurologists at Oregon Health and Science University (OR, USA) have demonstrated that α-synuclein plays a role in DNA repair and that disruption of this function may lead to neuronal cell death.
The paper, which has been published in Scientific Reports, suggests that the protein could be considered as a target for the treatment of Parkinson’s disease and other neurogenerative diseases.
In vitro immunocytochemical studies demonstrated that α-synuclein co-localizes with known DNA repair proteins, suggesting that it also plays a role in the repair of DNA.
Consequent experiments demonstrated that there was an increased incidence rate of DNA double-strand breaks in mice in which α-synuclein function had been impaired. Researchers anticipate that reintroduction of functional α-synuclein could rescue the severe DNA damage.
“This is the first time that anyone has discovered one of α-synuclein’s functions is DNA repair,” explained senior author, Vivek Unni (Oregon Health and Science University).
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In addition to this, introduction of Lewy bodies into neurons increased the number of DNA double strand breaks. The authors of the study suggest that aggregation of α-synuclein prevents it from accessing damaged DNA, inhibiting repair and ultimately leading to programmed cell death.
“It may be the loss of that function that’s killing that cell,” stated Unni. “That function is critical for cell survival, and it appears to be a function that’s lost in Parkinson’s disease.”
Unni commented that he hopes these findings lead to the development of methods to deliver α-synuclein proteins into the nucleus of cells or to the designing of methods to replace its function.
Sources: Schaser AJ, Osterberg VR, Dent SE et al. Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders. Sci. Rep. 9, 10919 (2019); www.eurekalert.org/pub_releases/2019-07/ohs-sra072519.php