Landreth Gary, Jiang Qingguang, Mandrekar Shweta, Heneka Michael
Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Neurotherapeutics. 2008 Jul;5(3):481-9. doi: 10.1016/j.nurt.2008.05.003.
Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid within the brain parenchyma and is accompanied by the impairment of neuronal metabolism and function, leading to extensive neuronal loss. The disease involves the perturbation of synaptic function, energy, and lipid metabolism. The development of amyloid plaques results in the induction of a microglial-mediated inflammatory response. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor whose biological actions are to regulate glucose and lipid metabolism and suppress inflammatory gene expression. Thus, agonists of this receptor represent an attractive therapeutic target for AD. There is now an extensive body of evidence that has demonstrated the efficacy of PPARgamma agonists in ameliorating disease-related pathology and improved learning and memory in animal models of AD. Recent clinical trials of the PPARgamma agonist rosiglitazone have shown significant improvement in memory and cognition in AD patients. Thus, PPARgamma represents an important new therapeutic target in treating AD.
阿尔茨海默病（AD）的特征是脑实质内β-淀粉样蛋白的沉积，并伴有神经元代谢和功能受损，导致广泛的神经元丢失。该疾病涉及突触功能、能量和脂质代谢的紊乱。淀粉样斑块的形成会引发小胶质细胞介导的炎症反应。核受体过氧化物酶体增殖物激活受体γ（PPARγ）是一种配体激活的转录因子，其生物学作用是调节葡萄糖和脂质代谢并抑制炎症基因表达。因此，该受体的激动剂是AD颇具吸引力的治疗靶点。现在有大量证据表明，PPARγ激动剂在改善AD动物模型中与疾病相关的病理状况以及提高学习和记忆能力方面具有疗效。PPARγ激动剂罗格列酮最近的临床试验表明，AD患者的记忆力和认知能力有显著改善。因此，PPARγ是治疗AD的一个重要新靶点。
