AUTHOR=Konopka Anna , Atkin Julie D. TITLE=The Role of DNA Damage in Neural Plasticity in Physiology and Neurodegeneration JOURNAL=Frontiers in Cellular Neuroscience VOLUME=16 YEAR=2022 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2022.836885 DOI=10.3389/fncel.2022.836885 ISSN=1662-5102 ABSTRACT=

Damage to DNA is generally considered to be a harmful process associated with aging and aging-related disorders such as neurodegenerative diseases that involve the selective death of specific groups of neurons. However, recent studies have provided evidence that DNA damage and its subsequent repair are important processes in the physiology and normal function of neurons. Neurons are unique cells that form new neural connections throughout life by growth and re-organisation in response to various stimuli. This “plasticity” is essential for cognitive processes such as learning and memory as well as brain development, sensorial training, and recovery from brain lesions. Interestingly, recent evidence has suggested that the formation of double strand breaks (DSBs) in DNA, the most toxic form of damage, is a physiological process that modifies gene expression during normal brain activity. Together with subsequent DNA repair, this is thought to underlie neural plasticity and thus control neuronal function. Interestingly, neurodegenerative diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington’s disease, manifest by a decline in cognitive functions, which are governed by plasticity. This suggests that DNA damage and DNA repair processes that normally function in neural plasticity may contribute to neurodegeneration. In this review, we summarize current understanding about the relationship between DNA damage and neural plasticity in physiological conditions, as well as in the pathophysiology of neurodegenerative diseases.