RNA Metabolism and DNA Stability in the Central Nervous System (CNS): From Aging to Neurodegenerative Disease

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Background

Aging, characterized by a gradual functional decline, is a major risk factor for most neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Common mechanisms underlying aging and neurodegeneration involve dysregulated RNA metabolism and genome instability. Altered gene expression and protein synthesis has been shown to be associated with aging, as well as age-associated neurodegeneration. Protein abnormalities and inclusion bodies are found to be accompanied with the aged brain. Defects in the regulation of RNA metabolism were also seen in neurodegenerative disorders by involving the mutation or mis-localization of RNA binding proteins leading to the formation of aggregation and inclusion of the proteins. In addition, growing evidence has shown that in the elderly and patients with neurodegeneration, the DNA damage, majorly caused by reactive oxygen species (ROS), is accumulated and DNA damage repair is deficient in both nuclei and mitochondria. Although dysregulated RNA metabolism and defective DNA damage repair have been linked to aging and neurodegeneration, the molecular mechanisms are not sufficiently investigated, which is critical to develop mechanism-based therapeutic avenues.

As we have known, currently, neither can aging be stopped, nor can neurodegenerative disease be cured. In addition to advancing our understanding on the mechanisms of the regulation on RNA transcription, splicing, and transportation in aging and neurodegeneration; the DNA damage repair in the mature neurons and their deficiency in neurodegeneration, this Research Topic may provide insights into potential therapeutic targets and contribute knowledge and ideas to develop methods for treatment.

This Research Topic welcomes any original research article, short report, review, and mini review regarding, but not limited to, the following research aspects:

• The regulation on RNA transcription, splicing and transportation in aging and neurodegeneration
• The molecular mechanisms of DNA damage repair in the mature neurons and their deficiency in both nuclei and mitochondria, in aging and neurodegeneration
• The mechanism of assembly and disassembly of RNA metabolism regulators on stress granules, and the consequent formation of pathological aggregation and inclusion bodies
• The involvement of DNA/RNA binding proteins in the formation and dissolving R-Loop as well as the repair of the DNA damage caused by which
• The signaling pathways that dysregulated RNA metabolism and DNA damage response lead to neurons death, for example, apoptosis and senescence
• RNA metabolism and DNA damage response in neuronal development

Keywords: RNA metabolism, DNA damage response, RNA binding proteins, Aging, Neurodegeneration

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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