Department of Biochemistry, University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi 110095, India.
King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
Curr Neuropharmacol. 2019;17(3):232-246. doi: 10.2174/1570159X16666180828100002.
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder, characterized by the deposition of amyloid-β within the brain parenchyma resulting in a significant decline in cognitive functions. The pathophysiological conditions of the disease are recognized by the perturbation of synaptic function, energy and lipid metabolism. In Addition deposition of amyloid plaques also triggers inflammation upon the induction of microglia. Peroxisome proliferatoractivated receptors (PPARs) are ligand-activated transcription factors known to play important role in the regulation of glucose absorption, homeostasis of lipid metabolism and are further known to involved in repressing the expression of genes related to inflammation. Therefore, agonists of this receptor represent an attractive therapeutic target for AD. Recently, both clinical and preclinical studies showed that use of Peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves both learning and memory along with other AD related pathology. Thus, PPARγ signifies a significant new therapeutic target in treating AD. In this review, we have shed some light on the recent progress of how, PPARγ agonist selectively modulated different cellular targets in AD and its amazing potential in the treatment of AD.
阿尔茨海默病（AD）是一种与年龄相关的进行性神经退行性疾病，其特征是淀粉样蛋白-β在脑实质中的沉积，导致认知功能显著下降。该疾病的病理生理状况被认为是突触功能、能量和脂质代谢的紊乱。此外，淀粉样斑块的沉积也会在小胶质细胞被诱导时引发炎症。过氧化物酶体增殖物激活受体（PPARs）是配体激活的转录因子，已知其在调节葡萄糖吸收、脂质代谢平衡方面发挥重要作用，并进一步参与抑制与炎症相关基因的表达。因此，该受体的激动剂是 AD 的一个有吸引力的治疗靶点。最近，临床前和临床研究都表明，过氧化物酶体增殖物激活受体γ（PPARγ）激动剂的使用改善了学习和记忆能力以及其他与 AD 相关的病理。因此，PPARγ在治疗 AD 方面是一个重要的新治疗靶点。在这篇综述中，我们阐述了 PPARγ 激动剂如何选择性地调节 AD 中不同的细胞靶点，以及它在治疗 AD 方面的巨大潜力。
