中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (8): 2264-2278.doi: 10.4103/NRR.NRR-D-24-00190

• 综述:退行性病与再生 • 上一篇    下一篇

糖酵解失调:阿尔茨海默病发病机制和治疗新靶点

  

  • 出版日期:2025-08-15 发布日期:2024-12-12

Glycolytic dysregulation in Alzheimer’s disease: unveiling new avenues for understanding pathogenesis and improving therapy

You Wu, Lijie Yang, Wanrong Jiang, Xinyuan Zhang, Zhaohui Yao*   

  1. Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
  • Online:2025-08-15 Published:2024-12-12
  • Contact: Zhaohui Yao, MD, yaozhaohui2004@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82271214 (to ZY) and the Natural Science Foundation of Hubei Province of China, No. 2022CFB109 (to ZY).

摘要:

阿尔茨海默病会导致认知能力逐渐下降,且目前缺乏治疗方法,这给阿尔茨海默病患者及社会带来了巨大挑战。目前的治疗策略主要基于胆碱酯酶抑制剂和 N-甲基-D-天冬氨酸受体拮抗剂,这些药物只能缓解症状,却无法阻止疾病的发展。目前的诊断缺乏非常客观的生物标志物,这是阿尔茨海默病的研究困境。最近的研究揭示了糖酵解这一大脑基本能量代谢途径在阿尔茨海默病发病机制中的关键作用。但是,这个主题还有待更新和总结。围绕着这个关键作用,文章首先总结了阿尔茨海默病中糖酵解的失调,然后详细介绍了阿尔茨海默病中,神经元的糖酵解增强、小胶质细胞的糖酵解增强、星形胶质细胞和少突胶质细胞中的糖酵解减弱以及神经元各细胞间糖酵解的串扰。文章结果不仅有助于深入认识阿尔茨海默病的发病机制,而且了解阿尔茨海默病中的糖酵解失调机制有助于从不同细胞的糖酵解改变的过程中找到诊断标志物和靶点,从而可以对阿尔茨海默病的诊断和治疗提供新的策略。

https://orcid.org/0000-0002-1276-9234 (Zhaohui Yao)

Abstract: Alzheimer’s disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists, offer limited symptomatic relief without halting disease progression, highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer’s disease. Recent studies have provided insights into the critical role of glycolysis, a fundamental energy metabolism pathway in the brain, in the pathogenesis of Alzheimer’s disease. Alterations in glycolytic processes within neurons and glial cells, including microglia, astrocytes, and oligodendrocytes, have been identified as significant contributors to the pathological landscape of Alzheimer’s disease. Glycolytic changes impact neuronal health and function, thus offering promising targets for therapeutic intervention. The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer’s disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression. Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer’s disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments, emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer’s disease.

Key words: Alzheimer’s disease, glial cells, glycolysis, neuronal metabolism, pathogenesis, therapeutic targets