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Metabolic Reprogramming-Driven Neuroimmunoregulation: Key Mechanisms and Therapeutic Opportunities and Challenges in
Nan Li1, Yuanyuan Wu2, Huiyi Feng2
1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China; School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Central nervous system (CNS) disorders involve immune and glial cell metabolic changes. This review synthesizes immunometabolic reprogramming across diseases, offering a framework to assess evidence strength and guide therapeutic development.
Area of Science:
- Neuroimmunology
- Metabolic pathways
- Central nervous system (CNS) disorders
Background:
- CNS disorders like Alzheimer's, Parkinson's, MS, and stroke are linked to metabolic issues in immune and glial cells.
- Aging influences glial-immune cell metabolism, affecting disease progression.
Purpose of the Study:
- To systematically review immunometabolic reprogramming in CNS diseases.
- To introduce an evidence-transparency framework for evaluating metabolic findings.
- To analyze the impact of aging on CNS immunometabolism.
Main Methods:
- Systematic synthesis of literature on glucose, lipid, amino acid metabolism, and oxidative phosphorylation.
- Application of an evidence-transparency framework to categorize supporting data (e.g., metabolic flux, molecular, genetic, human tissue).
- Analysis of aging's role and intercellular crosstalk in neuroinflammation and blood-brain barrier integrity.
Main Results:
- Identified convergent and divergent metabolic mechanisms across CNS diseases.
- Highlighted how aging modifies disease-specific metabolic reprogramming.
- Detailed shared translational obstacles for immunometabolic therapies.
Conclusions:
- A framework for interpreting immunometabolic evidence in CNS disorders is provided.
- Distinguishing correlative findings from causal mechanisms is crucial for therapeutic design.
- Targeting CNS immunometabolism requires addressing challenges like selectivity and blood-brain barrier penetration.
