中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (4): 708-715.doi: 10.4103/1673-5374.353484

• 综述:退行性病与再生 • 上一篇    下一篇

靶向神经炎症的阿尔茨海默病：从机制到临床应用

  


  • 出版日期:2023-04-15 发布日期:2022-10-27
  • 基金资助:
    国家自然科学基金面上项目(81971247）；国家社会科学基金重大项目（18ZDA215）; 浙江省自然科学基金（LQ22H310001）；浙江省2019重点研发计划（2020C03064）；浙江省教育厅一般科研项目（Y202146346）；宁波市“科技创新2025”重大专项（20181ZDYF020172）；宁波市自然科学基金（2021J101）

Targeting neuroinflammation in Alzheimer’s disease: from mechanisms to clinical applications

Zi-Zhen Si1, 2, #, Chen-Jun Zou3, #, Xi Mei4, Xiao-Fang Li5, Hu Luo5, Yao Shen6, Jun Hu3, Xing-Xing Li4, Lun Wu1, Yu Liu2, *   

  1. 1Pharmacy Department, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang Province, China; 2Department of Physiology and Pharmacology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, China; 3Department of Geriatric Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang Province, China;  4Key Laboratory Office of Sleep Medicine, Ningbo Kangning Hospital, Ningbo, Zhejiang Province, China;  5Department of Psychology, Collage of Teacher Education, Ningbo University, Ningbo, Zhejiang Province, China; 6Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, China 
  • Online:2023-04-15 Published:2022-10-27
  • Contact: Yu Liu, PhD, liuyu@nbu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81971247 (to YL), Zhejiang Provincial Key R & D Plan 2020, No. 2020C03064 (to YL), Ningbo R & D Plan, No. 20181ZDYF020172 (to YL), National Social Science Foundation Key Programs, No. 18ZDA215 (to YL), the Natural Science Foundation of Zhejiang Province, No. LQ22H310001 (to ZZS), the Natural Science Foundation of Ningbo, No. 2021J101 (to ZZS) and Regular Scientific Research Project of Education Department of Zhejiang Province, No. Y202146346 (to ZZS).

PDF

165

摘要：

阿尔茨海默病特点是持续的神经炎症，导致记忆丧失和认知能力下降。目前临床尚无有效的治疗方法可以阻止阿尔茨海默病的发展。越来越多的证据表明，神经炎症在阿尔茨海默病的发病机制中起着重要作用，同时还有经典的病理标志，如错误折叠和聚集的蛋白质（如淀粉样β蛋白和tau）。文章首先总结了阿尔茨海默病的临床和病理学特征。其次，概述了胶质细胞相关的炎症在阿尔茨海默病发病机制中的关键方面，并提供了小胶质细胞和星形细胞在阿尔茨海默病病理学中的作用的最新证据。然后，揭示了炎症细胞因子和炎症体在阿尔茨海默病中的双刃剑性质。此外，还通过这些机制讨论了先天免疫和神经炎症在阿尔茨海默病中的潜在治疗作用。最后，根据目前的研究现状，提出了未来需要解决的关键问题。

https://orcid.org/0000-0002-7581-5939 (Yu Liu)

Abstract: Alzheimer’s disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in Alzheimer’s disease research; however, no effective treatment is available to prevent disease progression. An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer’s disease pathogenesis, alongside the classical pathological hallmarks such as misfolded and aggregated proteins (e.g., amyloid-beta and tau). Firstly, this review summarized the clinical and pathological characteristics of Alzheimer’s disease. Secondly, we outlined key aspects of glial cell-associated inflammation in Alzheimer’s disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer’s disease pathology. Then, we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer’s disease. In addition, the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer’s disease were also discussed through these mechanisms. In the final section, the remaining key problems according to the current research status were discussed.

Key words: Alzheimer’s disease, astrocytes, immune signaling, inflammatory cytokines, microglia, neuroinflammation, neurotoxicity, therapeutic strategies