{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:19:01Z","timestamp":1793650741963,"version":"4.5.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>MicroRNAs (miRNAs) are small non-coding RNA molecules that are known to regulate gene expression in their target locations thereby contributing to epigenetic mechanisms associated with disease pathologies. Dysregulation of miRNA activity has been implicated in the pathology of Alzheimer\u2019s disease (AD), offering insights into potential biomarkers for early diagnosis and therapeutic targets. Mitochondrial dysfunction and its associated effects (such as oxidative stress) can be seen in early-onset AD. This review critically examines recent findings on mitochondrial-associated miRNAs\u2014including miR-34a, miR-140, miR-455-3p, and miR-1273g-3p\u2014highlighting their roles in mitochondrial bioenergetics, oxidative stress, and synaptic function. We discuss the therapeutic potential of targeting specific miRNAs to restore mitochondrial health and explore their utility as early biomarkers for AD diagnosis. A better understanding of miRNA-mediated mitochondrial regulation may open new avenues for early intervention in AD.<\/jats:p>","DOI":"10.3389\/fragi.2025.1582812","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T01:29:12Z","timestamp":1747099752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["miRNA mediated mitochondrial function and gene regulation associated with Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"6","author":[{"given":"Kumudu","family":"Subasinghe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1038\/s41388-023-02801-8","article-title":"A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy","volume":"42","author":"Abdelaal","year":"2023","journal-title":"Oncogene"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12581","DOI":"10.1523\/JNEUROSCI.3338-08.2008","article-title":"MicroRNA-338 regulates local CytochromecOxidase IV mRNA levels and oxidative phosphorylation in the axons of sympathetic neurons","volume":"28","author":"Aschrafi","year":"2008","journal-title":"J. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1010022","DOI":"10.1371\/journal.pcbi.1010022","article-title":"SPOROS: a pipeline to analyze DISE\/6mer seed toxicity","volume":"18","author":"Bartom","year":"2022","journal-title":"PLoS Comput. Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4362","DOI":"10.1038\/onc.2010.193","article-title":"Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression","volume":"29","author":"Chen","year":"2010","journal-title":"Oncogene"},{"key":"B5","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41392-024-02039-0","article-title":"Epigenetics-targeted drugs: current paradigms and future challenges","volume":"9","author":"Dai","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"110209","DOI":"10.18632\/oncotarget.22597","article-title":"MicroRNA-34a promotes mitochondrial dysfunction-induced apoptosis in human lens epithelial cells by targeting Notch2","volume":"8","author":"Fan","year":"2017","journal-title":"Oncotarget"},{"key":"B7","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/nature07823","article-title":"c-Myc suppression of miR-23a\/b enhances mitochondrial glutaminase expression and glutamine metabolism","volume":"458","author":"Gao","year":"2009","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1038\/s41416-020-0802-1","article-title":"Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours","volume":"122","author":"Hong","year":"2020","journal-title":"Br. J. Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"102459","DOI":"10.1016\/j.arr.2024.102459","article-title":"MicroRNA-455-3P as a peripheral biomarker and therapeutic target for mild cognitive impairment and Alzheimer's disease","volume":"100","author":"Islam","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/s41370-021-00306-8","article-title":"Longitudinal evaluation of whole blood miRNA expression in firefighters","volume":"31","author":"Jung","year":"2021","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.3390\/cells10102697","article-title":"Enhanced expression of microRNA-1273g-3p contributes to Alzheimer\u2019s disease pathogenesis by regulating the expression of mitochondrial genes","volume":"10","author":"Kim","year":"2021","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"102182","DOI":"10.1016\/j.redox.2021.102182","article-title":"MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: relevance to Alzheimer's disease","volume":"48","author":"Kumar","year":"2021","journal-title":"Redox Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"165937","DOI":"10.1016\/j.bbadis.2020.165937","article-title":"The role of synaptic microRNAs in Alzheimer's disease","volume":"1866","author":"Kumar","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/ncrna8010010","article-title":"A structural view of miRNA biogenesis and function","volume":"8","author":"Leit\u00e3o","year":"2022","journal-title":"Non-Coding RNA"},{"key":"B15","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/s41398-024-03075-8","article-title":"MicroRNAs: pioneering regulators in Alzheimer\u2019s disease pathogenesis, diagnosis, and therapy","volume":"14","author":"Li","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"135674","DOI":"10.1016\/j.neulet.2021.135674","article-title":"MicroRNA-140 silencing represses the incidence of Alzheimer's disease","volume":"758","author":"Liang","year":"2021","journal-title":"Neurosci. Lett."},{"key":"B17","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s12967-023-04037-2","article-title":"Identification of Timm13 protein translocase of the mitochondrial inner membrane as a potential mediator of liver fibrosis based on bioinformatics and experimental verification","volume":"21","author":"Liao","year":"2023","journal-title":"J. Transl. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1278334","DOI":"10.3389\/fncel.2023.1278334","article-title":"Role of microRNA-34a in blood\u2013brain barrier permeability and mitochondrial function in ischemic stroke","volume":"17","author":"Payne","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"742","DOI":"10.3390\/cells12050742","article-title":"Mitochondria localized microRNAs: an unexplored miRNA niche in alzheimer's disease and aging","volume":"12","author":"Rivera","year":"2023","journal-title":"Cells"},{"key":"B20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.brainres.2016.05.026","article-title":"Expression of microRNA-34a in Alzheimer's disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity","volume":"1646","author":"Sarkar","year":"2016","journal-title":"Brain Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s11064-022-03734-6","article-title":"Targeting novel microRNAs in developing novel alzheimer's disease treatments","volume":"48","author":"Seyedaghamiri","year":"2023","journal-title":"Neurochem. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1021\/acs.chemrestox.9b00090","article-title":"Formaldehyde, epigenetics, and alzheimer's disease","volume":"32","author":"Wang","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2025.1582812\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T01:29:12Z","timestamp":1747099752000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2025.1582812\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":23,"alternative-id":["10.3389\/fragi.2025.1582812"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2025.1582812","relation":{},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]},"article-number":"1582812"}}