{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:51:51Z","timestamp":1786121511370,"version":"build-2736575974"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Neurological diseases, often caused by irreversible loss of terminally differentiated neurons, present considerable challenges to treatment due to the limited regenerative capacity of these neurons. Although induced pluripotent stem cells hold promise for neuronal regeneration, their clinical application is constrained by risks, including tumorigenicity, incomplete neuronal maturation, and immune rejection. Recent advancements in direct neuronal reprogramming, which bypasses the intermediate pluripotent stage by directly converting non-neuronal cells into functional neurons, offer a compelling alternative for\n                    <jats:italic>in situ<\/jats:italic>\n                    neuronal replacement in neurodegenerative diseases. Key transcription factors, such as NeuroD1, Ascl1, Sox2, as well as CRISPR activation (CRISPRa) of NGN2 and ISL1, have been explored to convert glial cells into neurons. However, several challenges remain. This review discusses the current applications of direct neuronal reprogramming technology in several neurological diseases. We further highlight the potential contamination issues in adeno-associated virus (AAV) delivery systems and propose a code of conduct to avoid artifacts and pitfalls. Finally, we point out future directions for expanding direct reprogramming targets, integrating organoid-based disease modeling, and advancing reprogramming regulation techniques.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1889859","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:29:13Z","timestamp":1786080553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Direct neuronal reprogramming for neurological diseases: applications, translational Challenges, and future directions"],"prefix":"10.3389","volume":"20","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine, The Second Affiliated Hospital, Zhejiang University","place":["Hangzhou, China"]},{"name":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Medicine, The Second Affiliated Hospital, Zhejiang University","place":["Hangzhou, China"]},{"name":"Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Aging 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