{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:07Z","timestamp":1787028547239,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quinnipiac University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a common neurodegenerative disorder characterized by symptoms such as bradykinesia, resting tremor, and rigidity, primarily driven by the degradation of dopaminergic (DA) neurons in the substantia nigra. A significant contributor to familial autosomal dominant PD cases is mutations in the LRRK2 gene, making it a primary therapeutic target. This study explores the role of microRNAs (miRNAs) in regulating the proteomic stress responses associated with neurodegeneration in PD using C. elegans models. Our focus is on miR-71, a miRNA known to affect stress resistance and act as a pro-longevity factor in C. elegans. We investigated miR-71\u2019s function in C. elegans models of PD, where mutant LRRK2 expression correlates with dopaminergic neuronal death. Our findings reveal that miR-71 overexpression rescues motility defects and slows dopaminergic neurodegeneration in these models, suggesting its critical role in mitigating the proteotoxic effects of mutant LRRK2. Conversely, miR-71 knockout exacerbates neuronal death caused by mutant LRRK2. Additionally, our data indicate that miR-71\u2019s neuroprotective effect involves downregulating the toll receptor domain protein tir-1, implicating miR-71 repression of tir-1 as vital in the response to LRRK2-induced proteotoxicity. These insights into miR-71\u2019s role in C. elegans models of PD not only enhance our understanding of molecular mechanisms in neurodegeneration but also pave the way for potential research into human neurodegenerative diseases, leveraging the conservation of miRNAs and their targets across species.<\/jats:p>","DOI":"10.3390\/ijms25168795","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"8795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of TIR-1\/SARM-1 by miR-71 Protects Dopaminergic Neurons in a C. elegans Model of LRRK2-Induced Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-4935","authenticated-orcid":false,"given":"Devin","family":"Naidoo","sequence":"first","affiliation":[{"name":"Frank H. Netter MD School of Medicine, Quinnipiac University, North Haven, CT 06473, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-8515","authenticated-orcid":false,"given":"Alexandre","family":"de Lencastre","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Quinnipiac University, Hamden, CT 06518, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","unstructured":"Zafar, S., and Yaddanapudi, S.S. (2023). Parkinson Disease. StatPearls, StatPearls Publishing."},{"key":"ref_2","unstructured":"Stoker, T.B., and Greenland, J.C. (2018). Parkinson\u2019s Disease: Etiology, Neuropathology, and Pathogenesis. 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JoVE"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8795\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:35:46Z","timestamp":1760110546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,13]]},"references-count":45,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168795"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168795","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,13]]}}}