Landreth Gary
Department of Neurosciences, Case Western Reserve University, School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Curr Alzheimer Res. 2007 Apr;4(2):159-64. doi: 10.2174/156720507780362092.
Alzheimer's disease (AD) is a devastating neurodegenerative disease for which there are no highly effective therapies. A novel therapeutic approach to the treatment of AD is the use of agonists of the nuclear receptor, peroxisome proliferators-activated receptor gamma (PPARgamma). PPARgamma is a ligand activated transcription factor whose best described roles are to regulate lipid metabolism and inflammation. Agonists of PPARgamma have been shown to ameliorate AD-related pathology in animal models of AD and improve cognition. A number of potential mechanisms have been advanced to account for these effects. PPARgamma agonists act as insulin sensitizers, facilitating insulin action. In addition, PPARgamma agonists have been shown to inhibit inflammatory gene expression, alter Abeta homeostasis and exhibit neuroprotective effects. Importantly, recent clinical trials of FDA approved PPARgamma agonists have been shown to improve cognition and memory in AD patients. Thus, PPARgamma agonists represent a new and potentially efficacious treatment of AD.
阿尔茨海默病（AD）是一种毁灭性的神经退行性疾病，目前尚无高效疗法。一种治疗AD的新型方法是使用核受体过氧化物酶体增殖物激活受体γ（PPARγ）的激动剂。PPARγ是一种配体激活的转录因子，其最广为人知的作用是调节脂质代谢和炎症。在AD动物模型中，PPARγ激动剂已被证明可改善与AD相关的病理状况并提高认知能力。人们提出了许多潜在机制来解释这些作用。PPARγ激动剂可作为胰岛素增敏剂，促进胰岛素作用。此外，PPARγ激动剂已被证明可抑制炎症基因表达、改变β淀粉样蛋白（Aβ）的内稳态并发挥神经保护作用。重要的是，美国食品药品监督管理局（FDA）批准的PPARγ激动剂的近期临床试验已证明可改善AD患者的认知和记忆。因此，PPARγ激动剂代表了一种新的、可能有效的AD治疗方法。
