{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:36Z","timestamp":1787028576370,"version":"build-2736575974"},"reference-count":378,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIBR\u2019s core grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular RNAs are released from cells and circulate stably in biofluids such as blood, cerebrospinal fluid, saliva, and urine via carriers including extracellular vesicles, RNA-binding proteins and lipoproteins. Because transcriptional and metabolic disturbances\u2014notably mitochondrial dysfunction and oxidative stress\u2014often precede protein aggregation, synaptic loss, and structural change in many brain diseases, exRNAs offer minimally invasive access to early disease biology. Mechanistic studies demonstrate selective RNA packaging and delivery: transferred mRNAs can be translated and miRNAs can modulate targets, indicating exRNAs both report intracellular programs and actively influence recipient cells. Clinical and preclinical data support a dual role for exRNAs as biomarkers and as mediators of pathology. Key technical hurdles\u2014pre-analytical variability, isolation heterogeneity, and uncertain cellular origin\u2014limit reproducibility; recommended solutions include standardized workflows, carrier- and cell type-specific enrichment, multimodal integration with proteomics\/metabolomics and neuroimaging, and large, longitudinal validation studies. We synthesize mechanistic and clinical evidence for exRNA utility in early detection, prognosis, and therapeutic targeting and outline a roadmap to translate exRNA findings into robust clinical assays and interventions for neurodegenerative and brain disorders.<\/jats:p>","DOI":"10.3390\/ijms27010320","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Extracellular RNAs as Messengers and Early Biomarkers in Neurodegeneration"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6076-5176","authenticated-orcid":false,"given":"Kaidong","family":"Lu","sequence":"first","affiliation":[{"name":"College of Biological Sciences, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China"},{"name":"Chinese Institute for Brain Research, Beijing, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-4343","authenticated-orcid":false,"given":"Magdalena J.","family":"Koziol","sequence":"additional","affiliation":[{"name":"Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China"},{"name":"Chinese Institute for Brain Research, Beijing, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by Extracellular Vesicles: Where We Are and Where We Need to Go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41576-021-00346-8","article-title":"Examining the Evidence for Extracellular RNA Function in Mammals","volume":"22","author":"Gruner","year":"2021","journal-title":"Nat. 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