Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives.
Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives.
复制标题
对淀粉样蛋白-β 靶向治疗的批判性思考：挑战和观点。
DOI：
10.1007/s11427-020-1810-y
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Wang Yan-Jiang
中科院分区：
文献类型：
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作者：
Sun Bin-Lu;Chen Yang;Fan Dong-Yu;Zhu Chi;Zeng Fan;Wang Yan-Jiang
淀粉样蛋白β (a β)在阿尔茨海默病（AD）的发病机制中起着关键作用，一直被认为是AD的主要治疗靶点。然而，大多数针对a β的临床试验都没有成功。因此，a β靶向治疗这种复杂疾病的治疗策略需要重新评估。在这篇综述中，我们分析了当前抗a β治疗策略的挑战和关键点。除Aβ外，多种病理事件，如tau过度磷酸化、氧化应激和神经炎症，参与AD的发病机制并协同驱动疾病进展，可能是AD治疗的重要靶点。由于阿尔茨海默病的发病机制复杂且动态，三级预防策略是成功管理阿尔茨海默病的必要条件。从脑内外机制的系统视角，以及针对危险因素和合并症的多领域干预，是解决AD治疗的重要途径。
Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD) and has been regarded as the main therapeutic target for AD. However, most of the Aβ-targeted clinical trials have not succeeded. Therefore, the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated. In this review, we analyzed the challenges and critical points of the current anti-Aβ therapeutic strategies. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress, and neuroinflammation, which are involved in AD pathogenesis and synergistically drive disease progression, could be important targets for AD treatment. Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis. Systemic perspective addressing the disease pathogenesis within and outside the brain, as well as the multidomain intervention targeting risk factors and comorbidities, are important approaches for the therapeutic solutions of AD.