title: Energy dysfunction in Huntington's disease: insights from PGC-1α, AMPK, and CKB.
abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion in the Huntingtin (Htt) gene. When the number of CAG repeats exceeds 36, the translated polyglutamine-expanded Htt protein interferes with the normal functions of many types of cellular machinery and causes cytotoxicity. Clinical symptoms include progressive involuntary movement disorders, psychiatric signs, cognitive decline, dementia, and a shortened lifespan. The most severe brain atrophy is observed in the striatum and cortex. Besides the well-characterized neuronal defects, recent studies showed that the functions of mitochondria and several key players in energy homeostasis are abnormally regulated during HD progression. Energy dysregulation thus is now recognized as an important pathogenic pathway of HD. This review focuses on the importance of three key molecular determinants (peroxisome proliferator-activated receptor-γ coactivator-1α, AMP-activated protein kinase, and creatine kinase B) of cellular energy homeostasis and their possible involvement in HD pathogenesis.
authors.affiliation: Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan.
authors.forename: Tz-Chuen
authors.initials: TC
authors.lastname: Ju
authors.forename: Yow-Sien
authors.initials: YS
authors.lastname: Lin
authors.forename: Yijuang
authors.initials: Y
authors.lastname: Chern
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003401:Creatine / Q000627:therapeutic use; D052276:Creatine Kinase, BB Form / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004734:Energy Metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases; D052276:Creatine Kinase, BB Form; D003401:Creatine