Wu Zhidan, Boss Olivier
Novartis Institutes for BioMedical Research, Inc., 100 Technology Square, Cambridge, MA 02139, USA.
Expert Opin Ther Targets. 2007 Oct;11(10):1329-38. doi: 10.1517/14728222.11.10.1329.
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.
在世界大部分地区，2型糖尿病的患病率正以惊人的速度上升。迫切需要有效的治疗药物，不仅用于控制疾病，还用于预防或延缓其进展。从理论上讲，针对潜在发病机制的疗法可能具有这样的潜力。最近的证据有力地表明，线粒体功能受损是胰岛素抵抗和2型糖尿病潜在发病机制的一部分。过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）是一种转录共激活因子，在调节多个组织中的线粒体生物发生和能量代谢方面发挥关键作用。因此，通过激活PGC-1α来改善和恢复线粒体功能及氧化能力可为代谢疾病提供新的治疗方法。已证明多种蛋白质可调节PGC-1α的转录和/或活性，其中一些代表了有前景的药物干预靶点。
