Shaanxi Key Laboratory of Brain Disorders, Institute of Basic and Translational Medicine, Academician Workstation of Chen Zhi-nan Medical University, Xi'an Medical University, Xi'an 710021, China.
College of Pharmacy, Xi\'an Jiaotong University, Xi\'an 710049, China.
Curr Drug Targets. 2022;23(11):1040-1056. doi: 10.2174/1389450123666220421124030.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline. The obvious pathological features of AD are still amyloid plaques and neurofibrillary tangles. Development of disease-modifying treatments for AD has been challenging, with almost all drugs aborted. The amyloid cascade concept has been questioned due to the failures of various amyloid-targeting prospects. Despite this, targeting amyloid-β (Aβ) active immunotherapy provided some positive results to support this hypothesis and clinical trials of these candidates are ongoing. In this review, we describe the latest advance in therapeutic strategies based on amyloidogenic processing and evaluate the pros and cons of each treatment strategy. We also highlight the current status of the hottest immunotherapy and discuss the future development direction.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是记忆障碍和认知能力下降。AD 的明显病理特征仍然是淀粉样斑块和神经纤维缠结。由于各种针对淀粉样蛋白的药物都失败了,因此开发用于治疗 AD 的疾病修饰疗法一直具有挑战性。淀粉样蛋白级联假说因各种针对淀粉样蛋白的药物的失败而受到质疑。尽管如此,针对淀粉样蛋白-β(Aβ)的主动免疫疗法提供了一些积极的结果来支持这一假说,并且这些候选药物的临床试验正在进行中。在这篇综述中,我们描述了基于淀粉样蛋白生成加工的治疗策略的最新进展,并评估了每种治疗策略的优缺点。我们还强调了当前最热门的免疫疗法的现状,并讨论了未来的发展方向。