Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (8): 3387-3410.doi: 10.4103/NRR.NRR-D-25-00274

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Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy

Yun Chen1, #, Ping Yin2, #, Qianqian Chen2, Yangyang Zhang3, Yangyi Tang4, Weifeng Jin3, *, Li Yu1, 2, 5, *   

  1. 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou First People’s Hospital, Hangzhou, Zhejiang Province, China; 
    2School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China; 
    3School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China; 
    4The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China; 
    5Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, Zhejiang Province, China
  • Online:2026-08-18 Published:2026-04-25
  • Contact: Li Yu, PhD, yuli9119@126.com; Weifeng Jin, PhD, jin_weifeng@126.com.
  • Supported by:
    This work was supported by the Natural Science Foundation of Zhejiang Province of China, Nos. LZYQ25H270001 (to LY), LY24H270007 (to WJ); Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project, No. 2023ZR011 (to LY); China Postdoctoral Science Foundation, No. 2023TQ0295 (to LY); Postdoctoral Research Projects Merit-based Funding in Zhejiang Province (First-class funding), No. ZJ2023021 (to LY); and Xinmiao Talents Project of Zhejiang Province, No. 2024R410A022 (to YC).

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Abstract: Neurodegenerative diseases are a class of disorders with the gradual loss of the central nervous system and peripheral nervous system. Neurodegenerative diseases manifest primarily as cognitive and behavioral disorders that adversely affect the lives of millions of people worldwide. Therefore, it is necessary to elucidate the mechanism of neurodegenerative diseases further and find effective new therapies. In recent years, increasing evidence has shown that the immune system plays a significant role in the pathophysiology of neurodegenerative diseases and regulates this process. The central and peripheral immune systems exert different roles in the disease progression. The development of neurodegenerative diseases is influenced by interactions between them. This review focuses on how the immune system, including microglia mediated nucleotide-binding oligomerization domain-like receptor protein 3 inflammation activation and T cell-mediated neuroinflammation, interactions with neurodegenerative diseases by modulating protein aggregation and blood–brain barrier permeability. Besides, we gave particular attention to glial cell-centered multicellular interactions and the inflammatory signaling pathway. Insight into the immune system’s functions and cellular interactions is essential for progressing disease research. In addition, the functions and mechanisms of these immune cells also suggest new ideas and targets for treatment. Therefore, this review summarizes some of the existing treatment strategies for amyloid-beta, tau, neuroinflammation, α-synuclein, associated microbiota, immune modulation, and neural injury repair. In addition, this review summarizes and compares animal models of different common neurodegenerative diseases and clinical research progress. In view of the current research status, new research directions and suggestions are proposed.

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, immune system, multiple sclerosis, neurodegenerative diseases, Parkinson’s disease, pathogenic mechanism