CD33 in Alzheimer's Disease
CD33 in Alzheimer's Disease
复制标题
DOI：
10.1007/s12035-013-8536-1
复制
发表时间：
2014-02-01
影响因子：
5.1
通讯作者：
Tan, Lan
中科院分区：
文献类型：
--
作者：
Jiang, Teng;Yu, Jin-Tai;Tan, Lan
淀粉样β肽（Aβ）级联假说认为Aβ积累是阿尔茨海默病（AD）的根本引发因素，越来越多的证据表明Aβ清除受损而不是其过量产生是AD的主要致病事件。最近的遗传学研究已确定分化簇 33 (CD33) 是与 AD 相关的强遗传位点。 CD33作为I型跨膜蛋白，属于唾液酸结合免疫球蛋白样凝集素，介导细胞间相互作用并抑制免疫细胞的正常功能。在大脑中，CD33主要表达于小胶质细胞。研究发现 AD 大脑中 CD33 的水平升高，这与淀粉样蛋白斑块负荷和疾病严重程度呈正相关。更重要的是，CD33导致小胶质细胞介导的Aβ清除受损，从而导致大脑中淀粉样斑块的形成。在本文中，我们回顾了CD33与AD相关的最新流行病学发现，并讨论了CD33在该疾病中的水平和致病作用。基于CD33在AD发病机制中的贡献作用，靶向CD33可能为AD治疗策略提供新的机会。
The amyloid-beta peptide (A beta) cascade hypothesis posits that A beta accumulation is the fundamental initiator of Alzheimer's disease (AD), and mounting evidence suggests that impaired A beta clearance rather than its overproduction is the major pathogenic event for AD. Recent genetic studies have identified cluster of differentiation 33 (CD33) as a strong genetic locus linked to AD. As a type I transmembrane protein, CD33 belongs to the sialic acid-binding immunoglobulin-like lectins, mediating the cell-cell interaction and inhibiting normal functions of immune cells. In the brain, CD33 is mainly expressed on microglial cells. The level of CD33 was found to be increased in the AD brain, which positively correlated with amyloid plaque burden and disease severity. More importantly, CD33 led to the impairment of microglia-mediated clearance of A beta, which resulted in the formation of amyloid plaques in the brain. In this article, we review the recent epidemiological findings of CD33 that related with AD and discuss the levels and pathogenic roles of CD33 in this disease. Based on the contributing effects of CD33 in AD pathogenesis, targeting CD33 may provide new opportunities for AD therapeutic strategies.