Yuan Xiang-Zhen, Sun Sen, Tan Chen-Chen, Yu Jin-Tai, Tan Lan
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Qingdao Blood Center, Qingdao, China.
J Alzheimers Dis. 2017;58(2):303-322. doi: 10.3233/JAD-170061.
As a member of the A Disintegrin And Metalloproteinase (ADAM) family, ADAM10 has been identified as the constitutive α-secretase in the process of amyloid-β protein precursor (AβPP) cleavage and plays a critical role in reducing the generation of the amyloid-β (Aβ) peptides. Recent studies have demonstrated its beneficial role in alleviating the pathologic impairment in Alzheimer's disease (AD) both in vitro and in vivo. However, the role of ADAM10 in AD and the underlying molecular mechanisms are still not well established. Increasing evidence indicates that ADAM10 not only reduces the generation of Aβ but may also affect the pathology of AD through potential mechanisms including reducing tau pathology, maintaining normal synaptic functions, and promoting hippocampal neurogenesis and the homeostasis of neuronal networks. Mechanistically, ADAM10 regulates these functions by interacting with postsynaptic substrates in brain, especially synaptic cell receptors and adhesion molecules. Furthermore, ADAM10 protein in platelets seems to be a promising biomarker for AD diagnosis. This review will summarize the role of ADAM10 in AD and highlight its functions besides its role as the α-secretase in AβPP cleavage. Meanwhile, we will discuss the therapeutic potential of ADAM10 in treating AD.
作为解聚素和金属蛋白酶（ADAM）家族的一员，ADAM10已被确定为淀粉样β蛋白前体（AβPP）裂解过程中的组成型α-分泌酶，并在减少淀粉样β（Aβ）肽的生成中起关键作用。最近的研究表明，它在体外和体内减轻阿尔茨海默病（AD）的病理损伤方面具有有益作用。然而，ADAM10在AD中的作用及其潜在的分子机制仍未完全明确。越来越多的证据表明，ADAM10不仅减少Aβ的生成，还可能通过包括减少tau病理、维持正常突触功能、促进海马神经发生和神经网络稳态等潜在机制影响AD的病理过程。从机制上讲，ADAM10通过与大脑中的突触后底物相互作用来调节这些功能，尤其是突触细胞受体和黏附分子。此外，血小板中的ADAM10蛋白似乎是AD诊断的一个有前景的生物标志物。本综述将总结ADAM10在AD中的作用，并突出其在AβPP裂解中作为α-分泌酶之外的功能。同时，我们将讨论ADAM10在治疗AD方面的治疗潜力。
