Yang Luping, Jiang Yijing, Shi Lihong, Zhong Dongling, Li Yuxi, Li Juan, Jin Rongjiang
Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610037, China.
Rehabilitation Hospital affiliated to Fujian University of Traditional Chinese Medicine Fuzhou 350003 Fujian Key Laboratory of Rehabilitation Technology, Fuzhou 350003, China.
Curr Protein Pept Sci. 2020;21(1):66-77. doi: 10.2174/1389203720666190819142746.
Alzheimer's disease (AD) is the most common neurodegenerative disorder. The pathogenesis of AD is very complicated. For decades, the amyloid hypothesis has influenced and guided research in the field of AD. Meanwhile, researchers gradually realized that AD is caused by multiple concomitant factors, such as autophagy, mitochondrial quality control, insulin resistance and oxidative stress. In current clinical trials, the improvement strategies of AD, such as Aβ antibody immunotherapy and gamma secretase inhibitors, are limited. There is mounting evidence of neurodegenerative disorders indicated that activation of AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. We reviewed the researches on AMPK for AD, the results demonstrated that activation of AMPK is controversial in Aβ deposition and tau phosphorylation, but is positive to promote autophagy, maintain mitochondrial quality control, reduce insulin resistance and relieve oxidative stress. It is concluded that AMPK might be a new target for AD by aggressively treating the risk factors in the future.
阿尔茨海默病（AD）是最常见的神经退行性疾病。AD的发病机制非常复杂。几十年来，淀粉样蛋白假说一直影响并指导着AD领域的研究。与此同时，研究人员逐渐意识到AD是由多种伴随因素引起的，如自噬、线粒体质量控制、胰岛素抵抗和氧化应激。在当前的临床试验中，AD的改善策略，如Aβ抗体免疫疗法和γ-分泌酶抑制剂，都很有限。越来越多的神经退行性疾病证据表明，AMP激活蛋白激酶（AMPK）的激活可能具有广泛的神经保护作用。我们回顾了关于AMPK对AD的研究，结果表明，AMPK的激活在Aβ沉积和tau磷酸化方面存在争议，但在促进自噬、维持线粒体质量控制、降低胰岛素抵抗和减轻氧化应激方面具有积极作用。结论是，通过积极治疗未来的危险因素，AMPK可能成为AD的一个新靶点。
