The Therapeutic Potential of tRNA-derived Small RNAs in Neurodegenerative Disorders

Gene expressions and functions at various levels, namely post-transcriptional, transcriptional, and epigenetic, can be regulated by transfer RNA (tRNA)-derived small RNAs (tsRNAs), which are as well-established as tRNA fragments or tRFs. This regulation occurs when tsRNAs are created through the special endonuclease-mediated cleavage of mature or precursor tRNAs. However, tsRNAs are newly discovered entities, and molecular functions associated with tsRNAs are still not clearly understood. There is increasingly robust evidence suggesting that specific tsRNAs perform fundamental tasks in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders. Indeed, the patterns of tsRNA expression are uncertain and could be altered in patients suffering from Parkinson’s disease, pontocerebellar hypoplasia, amyotrophic lateral sclerosis, Alzheimer’s disease, and other neurodegenerative disorders. In the present article, a review is conducted of recent domestic and international progress in research on the potential cellular and molecular mechanisms of tsRNA biogenesis. We also describe endogenous tsRNAs during neuronal development and neurodegenerative disorders, thereby providing theoretical support and guidance for further revealing the therapeutic potential of tsRNAs in neurodegenerative disorders.