Ng Laura Lok-Haang, Chow Jessica, Lau Kwok-Fai
School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong SAR, China.
Biochem Soc Trans. 2024 Dec 19;52(6):2539-2556. doi: 10.1042/BST20241510.
The pathophysiological mechanism involving the proteolytic processing of amyloid precursor protein (APP) and the generation of amyloid plaques is of significant interest in research on Alzheimer's disease (AD). The increasing significance of the downstream AD-related pathophysiological mechanisms has sparked research interest in other products of the APP processing cascades, including the APP intracellular domain (AICD). The potential importance of AICD in various cellular processes in the central nervous system has been established through the identification of its interactors. The interaction between AICD and its physiological binding partners is implicated in cellular events including regulation of transcriptional activity, cytoskeletal dynamics, neuronal growth, APP processing and cellular apoptosis. On the contrary, AICD is also implicated in neurodegeneration, which is a potential outcome of the functional fluctuation of AICD-mediated neuronal processes within the neuronal network. In this review, we summarize the neuronal functions and pathological manifestations of the dynamic AICD interaction network.
涉及淀粉样前体蛋白（APP）蛋白水解加工及淀粉样斑块生成的病理生理机制，在阿尔茨海默病（AD）研究中备受关注。AD相关下游病理生理机制的重要性日益凸显，这引发了对APP加工级联反应其他产物的研究兴趣，包括APP细胞内结构域（AICD）。通过鉴定AICD的相互作用蛋白，已证实其在中枢神经系统各种细胞过程中的潜在重要性。AICD与其生理结合伙伴之间的相互作用涉及多种细胞事件，包括转录活性调节、细胞骨架动力学、神经元生长、APP加工及细胞凋亡。相反，AICD也与神经退行性变有关，这是AICD介导的神经元网络内神经元过程功能波动的潜在结果。在本综述中，我们总结了动态AICD相互作用网络的神经元功能和病理表现。
