Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology.
Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology.
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DOI：
10.1016/j.bbcan.2017.07.001
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Guo J;Cheng J;North BJ;Wei W
阿尔茨海默病（Alzheimer's disease，AD）是一种与衰老相关的神经退行性疾病，是人类痴呆的主要病因。过度磷酸化的tau蛋白介导的细胞内神经元缠结和淀粉样蛋白β介导的细胞外老年斑是AD的主要病理损害。与人类癌症相关的生长控制失调和大量基因突变不同，AD在没有基因组改变的情况下显示脑神经元的损伤和死亡。虽然各种生物学过程主要控制肿瘤发生，如炎症，代谢改变，氧化应激和胰岛素抵抗已与AD的发生，这些生物学过程和信号转导途径，包括mTOR，MAPK，SIRT，HIF和FOXO通路控制老化和AD的病理损伤的机制连接没有很好地概括。因此，我们进行了全面的审查，总结了这些关键的癌症相关信号通路在AD发病机制中的生理作用，包括这些通路与神经系统缠结和老年斑形成的串扰，以影响AD表型。重要的是，抗衰老和AD相关药物的药物研究也得到了强调。总之，在这篇综述中，我们讨论了癌症相关的信号通路可能在控制AD的发病机制中发挥的潜在作用，以及它们作为未来延缓或预防衰老相关疾病和对抗AD的靶向策略的潜力。
Alzheimer’s disease (AD) is an aging-related neurodegenerative disease and accounts for majority of human dementia. The hyper-phosphorylated tau-mediated intracellular neurofibrillary tangle and amyloid β-mediated extracellular senile plaque are characterized as major pathological lesions of AD. Different from the dysregulated growth control and ample genetic mutations associated with human cancers, AD displays damage and death of brain neurons in the absence of genomic alterations. Although various biological processes predominately governing tumorigenesis such as inflammation, metabolic alteration, oxidative stress and insulin resistance have been associated with AD genesis, the mechanistic connection of these biological processes and signaling pathways including mTOR, MAPK, SIRT, HIF, and the FOXO pathway controlling aging and the pathological lesions of AD are not well recapitulated. Hence, we performed a thorough review by summarizing the physiological roles of these key cancer-related signaling pathways in AD pathogenesis, comprising of the crosstalk of these pathways with neurofibrillary tangle and senile plaque formation to impact AD phenotypes. Importantly, the pharmaceutical investigations of anti-aging and AD relevant medications have also been highlighted. In summary, in this review, we discuss the potential role that cancer-related signaling pathways may play in governing the pathogenesis of AD, as well as their potential as future targeted strategies to delay or prevent aging-related diseases and combating AD.
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