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Although the underlying mechanisms by which mutant huntingtin causes neuronal dysfunction and degeneration have not been fully elucidated, compelling evidence suggests that mitochondrial dysfunction and compromised energy metabolism are key players in HD pathogenesis. Longitudinal studies of HD subjects have shown reductions in glucose utilization before the disease clinical onset. Preferential striatal neurodegeneration, a hallmark of HD pathogenesis, also has been associated with interrupted energy metabolism. Data from genetic HD models indicate that mutant huntingtin disrupts mitochondrial bioenergetics and prevents adenosine triphosphate (ATP) generation, implying altered energy metabolism as an important component of HD pathogenesis. Here we revisit the evidence of abnormal energy metabolism in the central nervous system of HD patients, review our current understanding of the molecular mechanisms underlying abnormal metabolism induced by mutant huntingtin, and discuss the promising therapeutic development by halting abnormal metabolism in HD. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25992","type":"journal-article","created":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T16:44:23Z","timestamp":1407948263000},"page":"1366-1374","source":"Crossref","is-referenced-by-count":41,"title":["Metabolism in HD: Still a relevant mechanism?"],"prefix":"10.1002","volume":"29","author":[{"given":"Wenzhen","family":"Duan","sequence":"first","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA"},{"name":"Department of Neuroscience Johns Hopkins University 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