Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Biomed Res Int. 2018 Oct 25;2018:3087475. doi: 10.1155/2018/3087475. eCollection 2018.
Neuroinflammation has been observed in association with neurodegenerative diseases including Alzheimer's disease (AD). In particular, a positive correlation has been documented between neuroinflammatory cytokine release and the progression of the AD, which suggests these cytokines are involved in AD pathophysiology. A histological hallmark of the AD is the presence of beta-amyloid (A) plaques and tau neurofibrillary tangles. Beta-amyloid is generated by the sequential cleavage of beta () and gamma () sites in the amyloid precursor protein (APP) by - and -secretase enzymes and its accumulation can result from either a decreased A clearance or increased metabolism of APP. Previous studies reported that neuroinflammatory cytokines reduce the efflux transport of A, leading to elevated A concentrations in the brain. However, less is known about the effects of neuroinflammatory mediators on APP expression and metabolism. In this article, we review the modulatory role of neuroinflammatory cytokines on APP expression and metabolism, including their effects on - and -secretase enzymes.
神经炎症与包括阿尔茨海默病（AD）在内的神经退行性疾病有关。特别是，已经有文献证明神经炎症细胞因子的释放与 AD 的进展之间存在正相关关系，这表明这些细胞因子参与了 AD 的病理生理学过程。AD 的一个组织学特征是β-淀粉样蛋白（A）斑块和 tau 神经原纤维缠结的存在。β-淀粉样蛋白是由β（）和γ（）位点在淀粉样前体蛋白（APP）中的顺序切割产生的，β-和γ-分泌酶酶，其积累可能是由于 A 清除减少或 APP 代谢增加所致。先前的研究报告称，神经炎症细胞因子会降低 A 的外排转运，导致大脑中 A 浓度升高。然而，对于神经炎症介质对 APP 表达和代谢的影响知之甚少。在本文中，我们综述了神经炎症细胞因子对 APP 表达和代谢的调节作用，包括它们对β-和γ-分泌酶的影响。
