中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (9): 4229-4230.doi: 10.4103/NRR.NRR-D-25-01144

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

胰高血糖素样肽-1受体激动剂调节神经炎症和神经发生

  

  • 出版日期:2026-09-15 发布日期:2026-05-11

Glucagon-like peptide-1 receptor agonists to modulate neuroinflammation and neurogenesis

Rosalie Elvira, Eng King Tan*, Zhi Dong Zhou*   

  1. National Neuroscience Institute of Singapore, Singapore (Elvira R, Tan EK, Zhou ZD)
    Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore (Tan EK, Zhou ZD)
    Department of Neurology, Singapore General Hospital, Singapore (Tan EK)
  • Online:2026-09-15 Published:2026-05-11
  • Contact: Zhi Dong Zhou, MD, PhD, zhidong.zhou@duke-nus.edu.sg; Eng King Tan, MD, Tan.eng.king@sgh.com.sg.
  • Supported by:
    This work was supported by the Open Fund Large Collaborative Grant (MOH‑OFLCG24may‑0004) and the Singapore Translational Research (STaR) Investigator Award (NMRC/STaR/0030/2018) (to EKT); the Open Fund‑Individual Research Grant (OF‑IRG, MOH‑001506), Clinician Scientist‑Individual Research Grants (CS‑IRG) (MOH‑001091, CIRG23jul‑0006), HLCA2024 (HLCA24Mar‑0019), and SingHealth‑Duke‑NUS Academic Medicine Position Grant (to ZDZ).

摘要: https://orcid.org/0000-0003-0251-4163 (Zhi Dong Zhou)
https://orcid.org/0000-0003-2977-9743 (Eng King Tan)

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed as drugs for type 2 diabetes and obesity, exhibit therapeutic effects for various neurological disorders recently, with multiple neuroprotective mechanisms. The GLP-1RAs therapy has been applied to acute ischemic stroke, where they limit neuroinflammation, stabilize the neurovascular unit, and reduce infarct volume. The GLP-1RAs drugs have also been tested for Wolfram syndrome, where they mitigate endoplasmic reticulum (ER) stress and inhibit neuronal apoptosis. Preclinical analyses demonstrate that GLP-1RAs can modulate neuroinflammation processes, including reprogramming of microglia towards antiinflammatory phenotypes, suppression of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation, suppressing pathological astrogliosis, and rebalance of peripheral immunity. Furthermore, GLP-1RAs were identified to enhance synaptic plasticity, improve cognitive deficits, and promote hippocampal neurogenesis via regulation of brain-derived neurotrophic factor/cAMP response element-binding protein (BDNF/CREB) and insulin-like growth factor 1 (IGF-1) pathways. However, embedded multimodal biomarkers (e.g., TREM2, neuroimaging, and neurogenesis markers) are required for further clinical translation and clinical trial investigation of target engagement, dosage optimization, and patient stratification. Future prioritizing mechanism-focused studies in the niche will help unlock the potential of GLP-1RAs as disease-modifying therapies for human neurological disorders.