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This study investigated the expression of key enzymes in this pathway in R6\/2 HD mice and human HD postmortem brain tissues. We further explored the therapeutic potential of modulating choline metabolism for HD. Both R6\/2 mice and HD patients exhibited reduced expression of glycerophosphocholine phosphodiesterase 1 (GPCPD1), a key enzyme in choline metabolism, in the striatum and cortex. The striatum of R6\/2 mice also showed decreased choline and phosphorylcholine, and increased glycerophosphocholine, suggesting disruption in choline metabolism due to GPCPD1 deficiency. Treatment with citicoline significantly improved motor performance, upregulated anti\u2010apoptotic Bcl2 expression, and reduced oxidative stress marker malondialdehyde in both brain regions. Metabolomic analysis revealed partial restoration of disrupted metabolic patterns in the striatum and cortex following citicoline treatment. These findings strongly suggest the role of GPCPD1 deficiency in choline metabolism dysregulation in HD. The therapeutic potential of citicoline in R6\/2 mice highlights the choline metabolic pathway as a promising target for future HD therapies.<\/jats:p>","DOI":"10.1111\/acel.14302","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T04:35:00Z","timestamp":1723696500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dysregulation of choline metabolism and therapeutic potential of citicoline in Huntington's disease"],"prefix":"10.1111","volume":"23","author":[{"given":"Kuo\u2010Hsuan","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital\u2010Linkou Medical Center Chang Gung University School of Medicine  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei\u2010Ling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Chang Gung University  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