Sundararajan Sophia, Jiang Qingguang, Heneka Michael, Landreth Gary
Department of Neurology, Case Western Reserve University, Cleveland, OH 44106-4928, United States.
Neurochem Int. 2006 Jul;49(2):136-44. doi: 10.1016/j.neuint.2006.03.020. Epub 2006 Jun 12.
Diseases of the central nervous system present a challenge for the development of new therapeutic agents. Nuclear receptors are ligand-activated transcription factors that have proven to be valuable targets for development of new drugs owing to their ability to directly regulate gene expression. The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), has been investigated for its action in ameliorating the development and progression of a number of CNS diseases. PPARgamma agonists exhibit potent anti-inflammatory effects and appear to have direct neuroprotective actions. PPARgamma agonists have been shown to be efficacious in animal models of Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis. The availability of FDA-approved agonists of this receptor will facilitate the rapid translation of these findings into clinical trials for a number of CNS diseases.
中枢神经系统疾病对新型治疗药物的研发构成挑战。核受体是配体激活的转录因子，由于其能够直接调节基因表达，已被证明是新药研发的重要靶点。核受体过氧化物酶体增殖物激活受体γ（PPARγ）在改善多种中枢神经系统疾病的发生和发展方面的作用已得到研究。PPARγ激动剂具有强大的抗炎作用，并且似乎具有直接的神经保护作用。PPARγ激动剂已在阿尔茨海默病、中风、多发性硬化症、帕金森病和肌萎缩侧索硬化症的动物模型中显示出疗效。这种受体的FDA批准激动剂的可得性将有助于将这些研究结果迅速转化为针对多种中枢神经系统疾病的临床试验。
