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The destabilisation of the SOD1 dimer is a key driving force in fALS and sALS. Protein aggregation resulting from the destabilised SOD1 is arrested by the clinical drug ebselen and its analogues (MR6-8-2 and MR6-26-2) by redeeming the stability of the SOD1 dimer. The in vitro target engagement of these compounds is demonstrated using the bimolecular fluorescence complementation assay with protein\u2013ligand binding directly visualised by co-crystallography in G93A SOD1. MR6-26-2 offers neuroprotection slowing disease onset of SOD1<jats:sup>G93A<\/jats:sup> mice by approximately 15\u00a0days. It also protected neuromuscular junction from muscle denervation in SOD1<jats:sup>G93A<\/jats:sup> mice clearly indicating functional improvement.<\/jats:p>","DOI":"10.1038\/s41598-024-62903-5","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T14:04:39Z","timestamp":1716818679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement"],"prefix":"10.1038","volume":"14","author":[{"given":"Seiji","family":"Watanabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangsa","family":"Amporndanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raheela","family":"Awais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Latham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Awais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"O\u2019Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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