The multiple roles of chronic stress and glucocorticoids in Alzheimer's disease pathogenesis.

IF 14.6 1区 医学 Q1 NEUROSCIENCES Trends in Neurosciences Pub Date : 2024-09-21 DOI:10.1016/j.tins.2024.08.015
Mia R Burke, Ioannis Sotiropoulos, Clarissa L Waites
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Abstract

Chronic stress and the accompanying long-term elevation of glucocorticoids (GCs), the stress hormones of the body, increase the risk and accelerate the progression of Alzheimer's disease (AD). Signatures of AD include intracellular tau (MAPT) tangles, extracellular amyloid β (Aβ) plaques, and neuroinflammation. A growing body of work indicates that stress and GCs initiate cellular processes underlying these pathologies through dysregulation of protein homeostasis and trafficking, mitochondrial bioenergetics, and response to damage-associated stimuli. In this review, we integrate findings from mechanistic studies in rodent and cellular models, wherein defined chronic stress protocols or GC administration have been shown to elicit AD-related pathology. We specifically discuss the effects of chronic stress and GCs on tau pathogenesis, including hyperphosphorylation, aggregation, and spreading, amyloid precursor protein (APP) processing and trafficking culminating in Aβ production, immune priming by proinflammatory cytokines and disease-associated molecular patterns, and alterations to glial cell and blood-brain barrier (BBB) function.

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慢性压力和糖皮质激素在阿尔茨海默病发病机制中的多重作用。
慢性压力和伴随而来的糖皮质激素(GCs)(人体的压力荷尔蒙)的长期升高会增加阿尔茨海默病(AD)的风险并加速其进展。阿尔茨海默病的特征包括细胞内 tau(MAPT)缠结、细胞外淀粉样β(Aβ)斑块和神经炎症。越来越多的研究表明,应激和 GCs 通过对蛋白质稳态和贩运、线粒体生物能以及对损伤相关刺激的反应的失调,启动了这些病症的细胞过程。在这篇综述中,我们整合了啮齿类动物和细胞模型机理研究的结果,其中明确的慢性应激方案或 GC 给药已被证明可诱发 AD 相关病理。我们特别讨论了慢性应激和 GCs 对 tau 发病机制的影响,包括高磷酸化、聚集和扩散,淀粉样前体蛋白 (APP) 加工和贩运最终导致 Aβ 生成,促炎细胞因子和疾病相关分子模式的免疫诱导,以及神经胶质细胞和血脑屏障 (BBB) 功能的改变。
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来源期刊
Trends in Neurosciences
Trends in Neurosciences 医学-神经科学
CiteScore
26.50
自引率
1.30%
发文量
123
审稿时长
6-12 weeks
期刊介绍: For over four decades, Trends in Neurosciences (TINS) has been a prominent source of inspiring reviews and commentaries across all disciplines of neuroscience. TINS is a monthly, peer-reviewed journal, and its articles are curated by the Editor and authored by leading researchers in their respective fields. The journal communicates exciting advances in brain research, serves as a voice for the global neuroscience community, and highlights the contribution of neuroscientific research to medicine and society.
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