中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 412-413.doi: 10.4103/1673-5374.179044

• 观点:退行性病与再生 • 上一篇    下一篇

载脂蛋白E2与阿尔茨海默病:到该仔细研究的时候了

  

  • 收稿日期:2016-01-18 出版日期:2016-03-15 发布日期:2016-03-15
  • 基金资助:

    作者由阿尔茨海默氏症协会研究者发起的研究资助(IIRG-10-172459)支持;由美国国立卫生研究院资助的机构发展奖(P20GM103418)、堪萨斯州阿尔茨海默氏病中心(P30AG035982)、堪萨斯大学研究所生殖健康与再生医学和堪萨斯一般研究和启动资金资助。

ApoE2 and Alzheimer’s disease: time to take a closer look

Long Wu, Liqin Zhao   

  1. Department of Pharmacology and Toxicology, School of Pharmacy(Wu L, Zhao L), Neuroscience Graduate Program, University of Kansas,Lawrence, KS, USA (Zhao L)
  • Received:2016-01-18 Online:2016-03-15 Published:2016-03-15
  • Contact: Liqin Zhao, Ph.D., lzhao@ku.edu.
  • Supported by:

    The authors are supported by the Alzheimer’s Association Investigator-Initiated Research Grant (IIRG-10-172459), the NIH-funded Institutional Development Award (P20GM103418), the NIH-funded University of Kansas Alzheimer’s Disease Center (P30AG035982), the University of Kansas Institute for Reproductive Health and Regenerative Medicine, and the University of Kansas general research and startup funds to LZ.

摘要:

人类脱辅基脂蛋白E(ApoE)是299-氨基酸蛋白质,其分子量是36 kDa。在末梢区域,ApoE主要存在于肝、肾和脾当中,ApoE在这些脏器的胆固醇和脂质传输及新陈代谢过程中发挥着举足轻重的作用。在中枢神经系统,ApoE由星形胶质细胞和小神经胶质综合及分泌,神经元也会分泌少量的ApoE。脑组织中的ApoE可用于损伤修复,具体是通过为神经元重新分配脂质以及通过调节轴突赘疣来实现。人类ApoE对碘氧基苯甲醚在阿尔茨海默病中的作用有所不同。ApoE3作为最普通的对碘氧基苯甲醚,在约75%的人体内都存在,ApoE3对阿尔茨海默病的作用是中立的。ApoE2相对较少,所占比率仅有5%,ApoE2是对阿兹海默氏症具有保护作用的变异体。在过去的20年当中,人们逐渐认识到ApoE2是一种保护性的变异体,然而,其根本机制尚不清晰。最近的发现提出了一个需要进一步深入研究的课题,通过这一课题可以加深我们对ApoE2机制的理解,使我们进一步了解ApoE基因与阿尔茨海默病相互作用的方式,从而采取相应的调整措施,保护老化的脑组织机能。进行这些机制研究得出的观点可能会用于研发治疗方案,旨在将老化的脑组织(尤其是携带ApoE4基因的脑组织)转换为类似携带ApoE2基因的脑组织,进而预防和降低患阿尔茨海默病的风险。

Abstract:

Alzheimer’s disease (AD) is the most common form of dementia among the elderly. It currently affects approximately 5.1 million Americans, a number predicted to triple by 2050. AD is clinically manifested as progressive loss of memory and cognitive function, and is characterized pathologically by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT). Since its discovery in 1906, extensive research has been undertaken to define AD pathogenesis and to develop treatments; however, the cause of AD remains largely unknown and no therapeutic success has been achieved in over 200 AD drug trials conducted in the past decade. These challenges underscore the need for increased research focus to better understand AD risk mechanisms that would allow for the development of strategies aimed at AD prevention and early intervention. In the past 20 years, ApoE2 has been increasingly recognized as a neuroprotective variant; however, the underlying mechanisms have been largely unexplored. Our recent findings offer new perspectives for further in-depth studies that will increase our understanding of the roles of ApoE2 and of how ApoE genotypes interact with sex to modulate the adaptation and defense mechanisms in the aging brain. The insights gained from these mechanistic investigations could potentially be translated into therapeutic strategies aimed to transform an aging —in particular, an ApoE4 brain—into an ApoE2-like brain, thereby preventing and reducing the risk for AD.