Majdi Alireza, Kamari Farzin, Vafaee Manouchehr Seyedi, Sadigh-Eteghad Saeed
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Rev Neurosci. 2017 Oct 26;28(7):767-781. doi: 10.1515/revneuro-2017-0008.
Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment.
大脑衰老过程复杂，其病理形式与学习和记忆功能障碍或认知损伤相关。在衰老过程中，胆碱能神经支配的变化以及乙酰胆碱能张力降低，可能会触发一系列参与氧化应激、兴奋毒性、淀粉样β蛋白毒性、细胞凋亡、神经炎症的分子途径，并扰乱大脑中的神经营养因子。尼古丁是烟碱型乙酰胆碱受体（nAChRs）的外源性激动剂，在nAChR表达调控中作为一种药理伴侣，可能干预导致病理变化的多种分子途径中的年龄相关变化。尽管尼古丁具有治疗潜力，但也有矛盾的效应报道，这可能归因于其倒U形剂量反应效应或药代动力学因素。此外，尼古丁给药应产生最佳治疗效果，而不会带来滥用潜力或毒性。总体而言，本综述旨在汇总关于尼古丁及其对认知相关机制和年龄相关认知损伤影响的既往和最新数据。
