Wu You, Yang Lijie, Jiang Wanrong, Zhang Xinyuan, Yao Zhaohui
Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Neural Regen Res. 2025 Aug 1;20(8):2264-2278. doi: 10.4103/NRR.NRR-D-24-00190. Epub 2024 Jul 29.
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-D-aspartate 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.
由于患者的认知功能进行性下降且缺乏治愈性治疗方法，阿尔茨海默病对全球健康构成了重大挑战。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，只能提供有限的症状缓解，无法阻止疾病进展，这凸显了迫切需要新的研究方向来解决阿尔茨海默病的关键潜在机制。最近的研究揭示了糖酵解（大脑中的一种基本能量代谢途径）在阿尔茨海默病发病机制中的关键作用。神经元和神经胶质细胞（包括小胶质细胞、星形胶质细胞和少突胶质细胞）内糖酵解过程的改变已被确定为阿尔茨海默病病理特征的重要促成因素。糖酵解变化影响神经元的健康和功能，因此为治疗干预提供了有前景的靶点。本综述的目的是整合当前关于与阿尔茨海默病相关的糖酵解改变的知识，并探讨这些异常导致疾病发生和进展的机制。全面关注糖酵解功能障碍影响阿尔茨海默病病理的途径，应能为潜在的治疗靶点和策略提供见解，为开创性治疗铺平道路，强调了在寻求对阿尔茨海默病的阐明和管理中理解代谢过程的重要性。
