Amyloid precursor protein (APP) is a transmembrane protein expressed largely within the central nervous system. Upon cleavage, it does not produce the toxic amyloid peptide (Aβ) only, which is involved in neurodegenerative progressions but via a non-amyloidogenic pathway it is metabolized to produce a soluble fragment (sAPPα) through α-secretase. While a lot of studies are focusing on the role played by APP in the pathogenesis of Alzheimer's disease, sAPPα is reported to have numerous neuroprotective effects and it is being suggested as a candidate with possible therapeutic potential against Alzheimer's disease. However, the mechanisms through which sAPPα precisely works remain elusive. We have presented a comprehensive review of how sAPPα is regulating the neuroprotective effects in different biological models. Moreover, we have focused on the role of sAPPα during different developmental stages of the brain, neurogenic microenvironment in the brain and how this metabolite of APP is regulating the neurogenesis which is regarded as a compelling approach to ameliorate the impaired learning and memory deficits in dementia and diseases like Alzheimer's disease. sAPPα exerts beneficial physiological, biochemical and behavioral effects mitigating the detrimental effects of neurotoxic compounds. It has shown to increase the proliferation rate of numerous cell types and promised the synaptogenesis, neurite outgrowth, cell survival and cell adhesion. Taken together, we believe that further studies are warranted to investigate the exact mechanism of action so that sAPPα could be developed as a novel therapeutic target against neuronal deficits.

中文翻译：

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破解可溶性淀粉样蛋白前体蛋白α（sAPPα）的神经保护和神经源性潜力。

淀粉样前体蛋白（APP）是一种跨膜蛋白，主要在中枢神经系统内表达。切割后，它不仅仅产生有毒的淀粉样肽（Aβ），它参与神经退行性进展，而是通过非淀粉样生成途径被代谢，通过α-分泌酶产生可溶性片段（sAPPα）。尽管许多研究都集中在APP在阿尔茨海默氏病发病机理中的作用上，但据报道sAPPα具有多种神经保护作用，并被建议作为对阿尔茨海默氏病具有潜在治疗潜力的候选药物。但是，sAPPα精确发挥作用的机制仍然难以捉摸。我们已经提出了关于sAPPα如何调节不同生物学模型中神经保护作用的全面综述。此外，我们集中研究了sAPPα在大脑不同发育阶段，大脑中的神经源性微环境中的作用，以及APP的这种代谢产物如何调节神经发生，这被认为是缓解痴呆症和疾病中受损的学习和记忆缺陷的有效方法像阿尔茨海默氏病。sAPPα发挥有益的生理，生化和行为作用，减轻了神经毒性化合物的有害作用。它已显示出增加许多细胞类型的增殖速率，并有望实现突触发生，神经突向外生长，细胞存活和细胞粘附。综上所述，我们认为有必要进行进一步的研究以研究确切的作用机制，从而使sAPPα可以发展成为针对神经元缺陷的新型治疗靶标。