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Laquinimod (LAQ) has been found to have therapeutic effects on multiple sclerosis and HD. However, the mechanism underlying LAQ's therapeutic effects remains unknown. Using HD mice that selectively express mutant huntingtin in oligodendrocytes and show demyelination, we found that LAQ reduces the Ser259 phosphorylation on myelin regulatory factor (MYRF), an oligodendrocyte\u2010specific transcription factor promoting the expression of myelin\u2010associated genes. The reduced MYRF phosphorylation inhibits MYRF's binding to mutant huntingtin and increases the expression of myelin\u2010associated genes. We also found that PRKG2, a cGMP\u2010activated protein kinase subunit II, promotes the Ser259\u2010MYRF phosphorylation and that knocking down PRKG2 increased myelin\u2010associated protein's expression in HD mice. Our findings suggest that PRKG2\u2010regulated phosphorylation of MYRF is involved in demyelination and can serve as a potential therapeutic target for reducing demyelination.<\/jats:p>","DOI":"10.15252\/embr.201949783","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T12:13:50Z","timestamp":1587125630000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Phosphorylation of myelin regulatory factor by PRKG2 mediates demyelination in Huntington's disease"],"prefix":"10.1038","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-6956","authenticated-orcid":false,"given":"Peng","family":"Yin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcheng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Jiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-6536","authenticated-orcid":false,"given":"Shihua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"BFEMBR201949783_CR1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s12264-013-1321-3","volume":"29","author":"AN Bankston","year":"2013","unstructured":"Bankston AN, Mandler MD, Feng Y (2013) Oligodendroglia and neurotrophic factors in neurodegeneration. 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