Futch Hunter S, Croft Cara L, Truong Van Q, Krause Eric G, Golde Todd E
Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.
Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.
Mol Neurodegener. 2017 Jun 21;12(1):49. doi: 10.1186/s13024-017-0190-z.
Alzheimer's Disease (AD) is the most prevalent progressive neurodegenerative disease; to date, no AD therapy has proven effective in delaying or preventing the disease course. In the search for novel therapeutic targets in AD, it has been shown that increased chronic psychologic stress is associated with AD risk. Subsequently, biologic pathways underlying psychologic stress have been identified and shown to be able to exacerbate AD relevant pathologies. In this review, we summarize the literature relevant to the association between psychologic stress and AD, focusing on studies investigating the effects of stress paradigms on transgenic mouse models of Amyloid-β (Aβ) and tau pathologies. In recent years, a substantial amount of research has been done investigating a key stress-response mediator, corticotropin-releasing hormone (CRH), and its interactions with AD relevant processes. We highlight attempts to target the CRH signaling pathway as a therapeutic intervention in these transgenic mouse models and discuss how targeting this pathway is a promising avenue for further investigation.
阿尔茨海默病（AD）是最常见的进行性神经退行性疾病；迄今为止，尚无AD疗法被证明能有效延缓或阻止疾病进程。在寻找AD的新型治疗靶点过程中，研究表明，慢性心理压力增加与AD风险相关。随后，心理压力背后的生物学途径已被确定，并显示能够加剧与AD相关的病理。在这篇综述中，我们总结了与心理压力和AD之间关联相关的文献，重点关注研究应激模式对淀粉样β蛋白（Aβ）和tau病理转基因小鼠模型影响的研究。近年来，已经开展了大量研究来调查一种关键的应激反应介质促肾上腺皮质激素释放激素（CRH）及其与AD相关过程的相互作用。我们强调在这些转基因小鼠模型中靶向CRH信号通路作为治疗干预的尝试，并讨论靶向该通路为何是进一步研究的一个有前景的途径。
