Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli, Uttar Pradesh, 226002, India.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli, Uttar Pradesh, 226002, India.
Med Chem. 2024;20(8):781-798. doi: 10.2174/0115734064295063240422100615.
Alzheimer's disease (AD) is a neurodegenerative disease leading to dementia because of complex phathomechanisms like amyloid β (Aβ) aggregation, tau aggregates, and neurofibrillary tangles. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported recently with neuroprotective and anti-inflammatory properties. PPARs belong to the superfamily of nuclear hormone receptors and function as ligand-activated transcription factors. These have emerged as crucial players in the pathogenesis of AD. This review presented the potential of PPARs and their agonists in treating neurodegenerative diseases like AD. PPARs regulate the expression of specific genes vital for synaptic function and neurotransmitter release. PPAR agonists play a critical role in increasing the clearance of Aβ peptides by lowdensity lipoprotein receptor-related protein 1 (LRP1) in the microvascular endothelial cells of the human brain. Studies have shown that PPAR agonists reduce the level of APoE-mRNA, contributing to the accumulation of Aβ plaques and up-regulation of PPAR. A knockout of miR-128 has been found to inhibit AD-like cognitive decline, amyloid precursor protein (APP) amyloidogenic processing, and inflammatory responses in AD. PPARs are involved in the pathomechanism of AD, and therefore, PPAR agonists could be viable options for controlling the neurodegenerative symptoms and may be useful in treating AD.
阿尔茨海默病（AD）是一种神经退行性疾病，由于淀粉样蛋白β（Aβ）聚集、tau 聚集和神经原纤维缠结等复杂的病理机制导致痴呆。最近有报道称，过氧化物酶体增殖物激活受体（PPAR）激动剂具有神经保护和抗炎特性。PPAR 属于核激素受体超家族，作为配体激活的转录因子发挥作用。这些已经成为 AD 发病机制中的关键因素。本文综述了 PPAR 及其激动剂在治疗 AD 等神经退行性疾病中的潜力。PPAR 调节与突触功能和神经递质释放有关的特定基因的表达。PPAR 激动剂在增加大脑微血管内皮细胞中低密度脂蛋白受体相关蛋白 1（LRP1）对 Aβ肽的清除中发挥着关键作用。研究表明，PPAR 激动剂降低了 APoE-mRNA 的水平，导致 Aβ斑块的积累和 PPAR 的上调。已经发现 miR-128 的敲除可以抑制 AD 样认知下降、淀粉样前体蛋白（APP）淀粉样形成加工和 AD 中的炎症反应。PPAR 参与了 AD 的发病机制，因此，PPAR 激动剂可能是控制神经退行性症状的可行选择，并可能对 AD 的治疗有用。
