{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:27:54Z","timestamp":1783711674128,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003663","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["RS-2023-00283779"],"award-info":[{"award-number":["RS-2023-00283779"]}],"id":[{"id":"10.13039\/501100003663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration with limited treatment options. In this study, we investigated the pathological role of microRNA-485-3p (miR-485-3p) in ALS, particularly its regulation of PGC-1\u03b1, a transcriptional coactivator essential for mitochondrial function and neuroprotection. We also evaluated the therapeutic potential of BMD-001S, a nanoparticle-based formulation encapsulating an antisense oligonucleotide targeting miR-485-3p. Our results demonstrated that miR-485-3p expression was significantly elevated in both SOD1G93A-expressing HMC3 microglial cells and in the spinal cords of SOD1G93A transgenic mice at late disease stages, implicating its contribution to ALS pathogenesis. Intravenous administration of BMD-001S effectively reduced miR-485-3p levels and restored PGC-1\u03b1 mRNA and PGC-1\u03b1 protein expression in the spinal cord. These molecular changes were associated with notable therapeutic outcomes, including reduced SOD1 protein aggregation, decreased neuroinflammation, and lower neurofilament light chain concentrations in cerebrospinal fluid. Moreover, BMD-001S treatment was associated with improvements in electrophysiological parameters and preservation of neuromuscular junction integrity during the observation period in SOD1G93A transgenic mice. Taken together, these findings suggest that miR-485-3p\/PGC-1\u03b1 pathway is a promising therapeutic target in ALS and support the potential of BMD-001S as a novel treatment strategy for the disease.<\/jats:p>","DOI":"10.3390\/ijms27020615","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:46:43Z","timestamp":1767786403000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of the miR-485-3p\/PGC-1\u03b1 Pathway by ASO-Loaded Nanoparticles Attenuates ALS Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-9326","authenticated-orcid":false,"given":"In Soo","family":"Ryu","sequence":"first","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-In","family":"Ha","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Joo","family":"Jung","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insun","family":"Kim","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Na","family":"Lim","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Su","family":"Min","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-9598","authenticated-orcid":false,"given":"Seung Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2529-9023","authenticated-orcid":false,"given":"Ilsang","family":"Yoon","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-1306","authenticated-orcid":false,"given":"Hyun-Jeong","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hyeob","family":"Ryu","sequence":"additional","affiliation":[{"name":"BIORCHESTRA Co., Ltd., 1, Gukjegwahak 2-ro, Yuseong-gu, Daejeon 34000, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","article-title":"Amyotrophic lateral sclerosis","volume":"344","author":"Rowland","year":"2001","journal-title":"N. 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