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REVIEW article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 16 - 2024 |
doi: 10.3389/fnagi.2024.1445470
Secretase promotes AD progression: simultaneously cleave Notch and APP
Provisionally accepted- 1 Shenyang Medical College, Shenyang, China
- 2 General Hospital of Northern Theater Command, shenyang, China
Alzheimer's disease (AD) involves complex pathological mechanisms. Secretases include membrane protein extracellular structural domain proteases and intramembrane proteases that cleave the topology to type I or type II. Secretases can effectively regulate the activation of Notch and amyloid precursor protein (APP), key factors in the progression of AD and cancer. This article systematically summarizes the intracellular localization, cleavage sites and products, and biological functions of six subtypes of secretases (α-secretase, β-secretase, γ-secretase, δ-secretase, ε-secretase, and ηsecretase), and for the first time, elucidates the commonalities and differences between these subtypes of secretases. We found that each subtype of secretase primarily cleaves APP and Notch as substrates, regulating Aβ levels through APP cleavage to impact the progression of AD, while also cleaving Notch receptors to affect cancer progression.Finally, we review the chemical structures, indications, and research stages of various secretase inhibitors, emphasizing the promising development of secretase inhibitors in the fields of cancer and AD.
Keywords: α, β, γ, δ, ε, η-secretase, Notch, Cancer, AD, APP
Received: 10 Jul 2024; Accepted: 31 Oct 2024.
Copyright: © 2024 Kefan, Zhang, Feng, Yao, Jia and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hui Jia, Shenyang Medical College, Shenyang, China
Ming-Sheng Zhou, Shenyang Medical College, Shenyang, China
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