{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:54:48Z","timestamp":1785354888298,"version":"3.55.0"},"reference-count":205,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Department of Education Project","award":["Y202248634"],"award-info":[{"award-number":["Y202248634"]}]},{"name":"Zhejiang Provincial Department of Education Project","award":["Y202454271"],"award-info":[{"award-number":["Y202454271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Non-coding RNAs have emerged as central regulators of gene expression in neurodegenerative diseases, offering new opportunities for diagnosis and therapy. This review synthesizes current knowledge on microRNAs, long non-coding RNAs, and circular RNAs in Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis, emphasizing their roles in synaptic function, proteostasis, mitochondrial biology, and neuroinflammation. We evaluate evidence supporting non-coding RNAs as circulating and tissue-based biomarkers for early detection, disease monitoring, and patient stratification, and we compare analytical platforms and biofluid sources. Mechanistic insights reveal how non-coding RNAs modulate pathogenic protein aggregation, neuronal excitability, immune cell crosstalk, and blood\u2013brain barrier integrity. Translational efforts toward RNA-targeted interventions are reviewed, including antisense oligonucleotides, small interfering RNAs, miRNA mimics and inhibitors, circular RNA decoys, and extracellular vesicle-mediated delivery systems. We discuss pharmacological modulation, delivery challenges, safety concerns, and strategies to enhance specificity and CNS penetration. Finally, we outline emerging computational and multi-omics approaches to prioritize therapeutic targets and propose a roadmap for advancing non-coding RNA research from preclinical models to clinical trials. Addressing biological heterogeneity and delivery barriers will be pivotal to realizing the diagnostic and therapeutic promise of the non-coding transcriptome in neurodegenerative disease. Collaboration across disciplines and rigorous clinical validation are urgently needed.<\/jats:p>","DOI":"10.3390\/ph19010092","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T16:07:07Z","timestamp":1767629227000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets"],"prefix":"10.3390","volume":"19","author":[{"given":"Xuezhi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Gynecology, Women\u2019s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongquan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Women\u2019s Hospital, School of Medicine, Zhejiang University, No. 1 Xueshi Road, Shangcheng District, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-2967","authenticated-orcid":false,"given":"Xiaoyu","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Affiliated Hangzhou First People\u2019s Hospital, School of Medicine, Westlake University, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4560-6861","authenticated-orcid":false,"given":"Yao","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Women\u2019s Hospital, School of Medicine, Zhejiang University, No. 1 Xueshi Road, Shangcheng District, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8858-7388","authenticated-orcid":false,"given":"Dongxu","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Women\u2019s Hospital, School of Medicine, Zhejiang University, No. 1 Xueshi Road, Shangcheng District, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2024). 2024 Alzheimer\u2019s disease facts and figures. 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