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We here identified tsRNA profiles within susceptible tissues in animal models of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) to pinpoint disease-specific tsRNAs and those shared across neurodegenerative diseases. We performed small RNA sequencing in the SOD1G93A and TDP43A315T mouse models of ALS (spinal cord), the TauP301S model of FTD (hippocampus), and the parkin\/POLG model of PD (substantia nigra). Bioinformatic analysis showed higher expression of 5\u2032 tiRNAs selectively in the two ALS models, lower expression of 3\u2032 tRFs in both the ALS and FTD mouse models, and lower expression of itRF Arg in the PD model. Experimental validation confirmed the expression of tsRNAs. Gene Ontology analysis of targets associated with validated 3\u2032 tRFs indicated functions in the regulation of synaptic and neuronal pathways. Our profiling of tsRNAs indicates disease-specific fingerprints in animal models of neurodegeneration, which require validation in human disease.<\/jats:p>","DOI":"10.1242\/dmm.050870","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T07:57:38Z","timestamp":1731916658000},"source":"Crossref","is-referenced-by-count":11,"title":["Distinct fingerprints of tRNA-derived small non-coding RNA in animal models of neurodegeneration"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-7964","authenticated-orcid":false,"given":"Sharada","family":"Baindoor","sequence":"first","affiliation":[{"name":"Royal College of Surgeons in Ireland 1 Department of Physiology and Medical Physics , , 123 St Stephen's Green, Dublin D02 YN77 ,","place":["Ireland"]},{"name":"FutureNeuro SFI Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland 2 , Dublin D02 YN77 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-1570","authenticated-orcid":false,"given":"Hesham A. 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