Targeting PGC-1 alpha to control energy homeostasis.
The prevalence of Type 2 diabetes is increasing at an alarming rate in most parts of the world. Effective therapeutic drugs are urgently needed, not only to control the disease but also to prevent or delay its progression. Therapies that target the underlying pathogenesis could, in theory, hold such potential. Recent evidence strongly suggests that impaired mitochondrial function is part of the underlying pathogenesis of insulin resistance and Type 2 diabetes. Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1alpha) is a transcription co-activator that plays a key role in regulating mitochondrial biogenesis and energy metabolism in multiple tissues. Thus, improvement and restoration of mitochondrial function and oxidative capacity through activation of PGC-1alpha could provide new treatments for metabolic diseases. A diverse array of proteins has been shown to regulate PGC-1alpha transcription and/or activity, some of which represent promising targets for pharmaceutical intervention.
Wu
Zhidan
Z
Novartis Institutes for BioMedical Research, Inc., 100 Technology Square, Cambridge, MA 02139, USA. zhidan.wu@novartis.com
Boss
Olivier
O
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors