Saeedi Saravi Seyed Soheil, Saeedi Saravi Seyed Sobhan, Arefidoust Alireza, Dehpour Ahmad Reza
Department of Toxicology-Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Metab Brain Dis. 2017 Aug;32(4):949-965. doi: 10.1007/s11011-017-0021-5. Epub 2017 Jun 3.
Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties. Despite the voluminous literature on the clinical advantages of 3-hydroxy-3-methylglutaryl Co-enzyme A reductase (HMGCR) inhibitors (statins) in cardiovascular system, the neuroprotective effects and the underlying mechanisms are little understood. Hence, the present review tries to provide a critical overview on the statin-induced neuroprotection, which are presumed to be associated with the ability to reduce cholesterol, Amyloid-β and apolipoprotein E (ApoE) levels, decrease reactive oxygen and nitrogen species (ROS and RNS) formation, inhibit excitotoxicity, modulate matrix metalloproteinases (MMPs), stimulate endothelial nitric oxide synthase (eNOS), and increase cerebral blood perfusion. This review is also aimed to illustrate that statins protect neurons against the neuro-inflammatory processes through balancing pro-inflammatory/anti-inflammatory cytokines. Ultimately, the beneficial role of statins in ameliorating the development of PD, AD, MS and cerebral ischemic stroke has been separately reviewed.
他汀类药物,即降胆固醇药物,已被证明除了其原始作用外,在其他病症中也能发挥有益作用,如原发性和进展性神经退行性疾病。观察发现他汀类药物可改善帕金森病(PD)、阿尔茨海默病(AD)、多发性硬化症(MS)和脑缺血性中风等神经退行性疾病,这些药物的神经保护作用被认为与其抗炎、抗氧化和抗兴奋毒性特性有关。尽管关于3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)抑制剂(他汀类药物)在心血管系统中的临床优势已有大量文献报道,但对其神经保护作用及潜在机制却知之甚少。因此,本综述试图对他汀类药物诱导的神经保护作用进行批判性概述,这些作用被认为与降低胆固醇、β-淀粉样蛋白和载脂蛋白E(ApoE)水平、减少活性氧和氮物种(ROS和RNS)形成、抑制兴奋毒性、调节基质金属蛋白酶(MMPs)、刺激内皮型一氧化氮合酶(eNOS)以及增加脑血流量的能力有关。本综述还旨在说明他汀类药物通过平衡促炎/抗炎细胞因子来保护神经元免受神经炎症过程的影响。最终,分别综述了他汀类药物在改善PD、AD、MS和脑缺血性中风发展方面的有益作用。