PKM2-mediated metabolic reprogramming of microglia in neuroinflammation

Abstract Microglia, the resident immune cells of the central nervous system, undergo metabolic reprogramming during neuroinflammation, playing a crucial role in the pathogenesis of neurological disorders such as Parkinson’s disease. This review focuses on Pyruvate Kinase M2 (PKM2), a key glycolytic...

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Main Authors: Qi Zhang, Sha-Sha Wang, Zhao Zhang, Shi-Feng Chu
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02453-5
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author Qi Zhang
Sha-Sha Wang
Zhao Zhang
Shi-Feng Chu
author_facet Qi Zhang
Sha-Sha Wang
Zhao Zhang
Shi-Feng Chu
author_sort Qi Zhang
collection DOAJ
description Abstract Microglia, the resident immune cells of the central nervous system, undergo metabolic reprogramming during neuroinflammation, playing a crucial role in the pathogenesis of neurological disorders such as Parkinson’s disease. This review focuses on Pyruvate Kinase M2 (PKM2), a key glycolytic enzyme, and its impact on microglial metabolic reprogramming and subsequent neuroinflammation. We explore the regulatory mechanisms governing PKM2 activity, its influence on microglial activation and immune responses, and its contribution to the progression of various neurological diseases. Finally, we highlight the therapeutic potential of targeting PKM2 as a novel strategy for treating neuroinflammation-driven neurological disorders. This review provides insights into the molecular mechanisms of PKM2 in neuroinflammation, aiming to inform the development of future therapeutic interventions.
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series Cell Death Discovery
spelling doaj-art-7eb6ea1e0dc7401c97f69f5129b49a3a2025-08-20T01:53:23ZengNature Publishing GroupCell Death Discovery2058-77162025-04-011111810.1038/s41420-025-02453-5PKM2-mediated metabolic reprogramming of microglia in neuroinflammationQi Zhang0Sha-Sha Wang1Zhao Zhang2Shi-Feng Chu3Basic medicine college, China Three Gorges UniversityState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBasic medicine college, China Three Gorges UniversityAbstract Microglia, the resident immune cells of the central nervous system, undergo metabolic reprogramming during neuroinflammation, playing a crucial role in the pathogenesis of neurological disorders such as Parkinson’s disease. This review focuses on Pyruvate Kinase M2 (PKM2), a key glycolytic enzyme, and its impact on microglial metabolic reprogramming and subsequent neuroinflammation. We explore the regulatory mechanisms governing PKM2 activity, its influence on microglial activation and immune responses, and its contribution to the progression of various neurological diseases. Finally, we highlight the therapeutic potential of targeting PKM2 as a novel strategy for treating neuroinflammation-driven neurological disorders. This review provides insights into the molecular mechanisms of PKM2 in neuroinflammation, aiming to inform the development of future therapeutic interventions.https://doi.org/10.1038/s41420-025-02453-5
spellingShingle Qi Zhang
Sha-Sha Wang
Zhao Zhang
Shi-Feng Chu
PKM2-mediated metabolic reprogramming of microglia in neuroinflammation
Cell Death Discovery
title PKM2-mediated metabolic reprogramming of microglia in neuroinflammation
title_full PKM2-mediated metabolic reprogramming of microglia in neuroinflammation
title_fullStr PKM2-mediated metabolic reprogramming of microglia in neuroinflammation
title_full_unstemmed PKM2-mediated metabolic reprogramming of microglia in neuroinflammation
title_short PKM2-mediated metabolic reprogramming of microglia in neuroinflammation
title_sort pkm2 mediated metabolic reprogramming of microglia in neuroinflammation
url https://doi.org/10.1038/s41420-025-02453-5
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