Hottman David A, Chernick Dustin, Cheng Shaowu, Wang Zhe, Li Ling
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Neurobiol Dis. 2014 Dec;72 Pt A:22-36. doi: 10.1016/j.nbd.2014.07.015. Epub 2014 Aug 13.
High-density lipoproteins (HDLs) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function.
高密度脂蛋白(HDL)是由各种脂质和蛋白质组成的一组异质性脂蛋白。HDL在体循环和大脑中均有形成。除了在逆向胆固醇转运途径中起关键作用外,HDL还具有广泛的其他功能,包括抗氧化、抗炎、促进内皮功能、抗血栓形成以及调节免疫功能。血浆HDL水平高可预防心血管疾病,这一点已得到确凿证实。越来越多的证据表明,HDL的有益作用扩展到包括中枢神经系统在内的许多其他系统。认知是一种复杂的脑功能,包括感知、思维和记忆的各个方面。认知功能在衰老过程中常常下降,这种下降在诸如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症等与年龄相关的进行性神经退行性疾病中表现为认知障碍/痴呆。目前令人日益担忧的是,尚无有效的疗法可预防或治疗这些毁灭性疾病。新出现的证据表明,HDL可能在正常和病理条件下维持认知功能方面发挥关键作用。本综述试图总结近期关于HDL对衰老和神经退行性疾病中认知影响的遗传学、临床和实验证据,以及HDL增强方法改善认知功能的潜力。