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阿尔茨海默病免疫及免疫治疗的机制性研究方法:综述

Mechanistic Approach to Immunity and Immunotherapy of Alzheimer's Disease: A Review.

作者信息

Islam Md Rubiath, Rabbi Md Afser, Hossain Tanbir, Sultana Sadia, Uddin Shihab

机构信息

Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.

Department of Bioengineering, King Fahad University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia.

出版信息

ACS Chem Neurosci. 2024 Aug 22. doi: 10.1021/acschemneuro.4c00360.

Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative condition characterized by progressive cognitive decline and memory loss, affecting millions of people worldwide. Traditional treatments, such as cholinesterase inhibitors and NMDA receptor antagonists, offer limited symptomatic relief without addressing the underlying disease mechanisms. These limitations have driven the development of more potent and effective therapies. Recent advances in immunotherapy present promising avenues for AD treatment. Immunotherapy strategies, including both active and passive approaches, harness the immune system to target and mitigate AD-related pathology. Active immunotherapy stimulates the patient's immune response to produce antibodies against AD-specific antigens, while passive immunotherapy involves administering preformed antibodies or immune cells that specifically target amyloid-β (Aβ) or tau proteins. Monoclonal antibodies, such as aducanumab and lecanemab, have shown potential in reducing Aβ plaques and slowing cognitive decline in clinical trials, despite challenges related to adverse immune responses and the need for precise targeting. This comprehensive review explores the role of the immune system in AD, evaluates the current successes and limitations of immunotherapeutic approaches, and discusses future directions for enhancing the treatment efficacy.

摘要

阿尔茨海默病(AD)是一种使人衰弱的神经退行性疾病,其特征是进行性认知衰退和记忆丧失,影响着全球数百万人。传统治疗方法,如胆碱酯酶抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂,只能提供有限的症状缓解,无法解决潜在的疾病机制。这些局限性推动了更有效疗法的开发。免疫疗法的最新进展为AD治疗提供了有前景的途径。免疫疗法策略,包括主动和被动方法,利用免疫系统来靶向和减轻与AD相关的病理。主动免疫疗法刺激患者的免疫反应以产生针对AD特异性抗原的抗体,而被动免疫疗法则涉及施用预先形成的抗体或特异性靶向淀粉样β蛋白(Aβ)或tau蛋白的免疫细胞。单克隆抗体,如阿杜卡单抗和仑卡奈单抗,尽管存在与不良免疫反应相关的挑战以及精确靶向的需求,但在临床试验中已显示出减少Aβ斑块和减缓认知衰退的潜力。这篇综述探讨了免疫系统在AD中的作用,评估了免疫治疗方法目前的成功与局限性,并讨论了提高治疗效果的未来方向。

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