title: PGC-1α, mitochondrial dysfunction, and Huntington's disease.
abstract: The constant high energy demand of neurons makes them rely heavily on their mitochondria. Dysfunction of mitochondrial energy metabolism leads to reduced ATP production, impaired calcium buffering, and generation of reactive oxygen species. There is strong evidence that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Huntington's disease (HD). Studies over the past few years have implicated an impaired function of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional master coregulator of mitochondrial biogenesis, metabolism, and antioxidant defenses, in causing mitochondrial dysfunction in HD. Here we have attempted to discuss in a nutshell, the key findings on the role of PGC-1α in mitochondrial dysfunction in HD and its potential as a therapeutic target to cure HD.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10065, USA. Electronic address: johri.ashu@gmail.com.
authors.forename: Ashu
authors.initials: A
authors.lastname: Johri
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: M
authors.initials: M
authors.lastname: Flint Beal
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: 3-NP; 3-nitropropionic acid; 4-hydroxynonenal; 8-OHdG; 8-hydroxy-2′-deoxyguanosine; BAT; Energy metabolism; HD; HNE; Huntington's disease; MBP; MDA; Mitochondrial dynamics; Mitochondrial dysfunction; Mitophagy; NOXNADPH; Neurodegeneration; OXPHOS; Oxidative stress; PGC-1α; PPAR; PPARs; ROS; SIRT1; SIRT3; Therapeutics; brown adipose tissue; malondialdehyde; myelin basic protein; oxidase; oxidative phosphorylation; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor-γ coactivator-1α; reactive oxygen species