Wu Jiale, Tang Jun, Huang Di, Wang Yu, Zhou Enyuan, Ru Qin, Xu Guodong, Chen Lin, Wu Yuxiang
Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan, China.
Front Aging Neurosci. 2024 Nov 25;16:1482947. doi: 10.3389/fnagi.2024.1482947. eCollection 2024.
Sarcopenia and AD are both classic degenerative diseases, and there is growing epidemiological evidence of their comorbidity with aging; however, the mechanisms underlying the biology of their commonality have not yet been thoroughly investigated. APP is a membrane protein that is expressed in tissues and is expressed not only in the nervous system but also in the NMJ and muscle. Deposition of its proteolytic cleavage product, Aβ, has been described as a central component of AD pathogenesis. Recent studies have shown that excessive accumulation and aberrant expression of APP in muscle lead to pathological muscle lesions, but the pathogenic mechanism by which APP and its proteolytic cleavage products act in skeletal muscle is less well understood. By summarizing and analyzing the literature concerning the role, pathogenicity and pathological mechanisms of APP and its cleavage products in the nervous system and muscles, we aimed to explore the intrinsic pathological mechanisms of myocerebral comorbidities and to provide new perspectives and theoretical foundations for the prevention and treatment of AD and sarcopenia comorbidities.
肌少症和阿尔茨海默病（AD）都是典型的退行性疾病，并且有越来越多的流行病学证据表明它们在衰老过程中共存；然而，它们共性生物学背后的机制尚未得到充分研究。淀粉样前体蛋白（APP）是一种在组织中表达的膜蛋白，不仅在神经系统中表达，在神经肌肉接头和肌肉中也有表达。其蛋白水解裂解产物β淀粉样蛋白（Aβ）的沉积被认为是AD发病机制的核心组成部分。最近的研究表明，APP在肌肉中的过度积累和异常表达会导致病理性肌肉损伤，但APP及其蛋白水解产物在骨骼肌中发挥作用的致病机制尚不太清楚。通过总结和分析关于APP及其裂解产物在神经系统和肌肉中的作用、致病性和病理机制的文献，我们旨在探索肌脑共病的内在病理机制，并为AD和肌少症共病的预防和治疗提供新的视角和理论基础。
