Microglial Metabolic Reprogramming: Emerging Insights and Therapeutic Strategies in Neurodegenerative Diseases
Jifei Miao1,2, Lihua Chen1, Xiaojin Pan1
1Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, China.
Abstract:
Microglia, the resident immune cells of the central nervous system, play a critical role in maintaining brain homeostasis. However, in neurodegenerative conditions, microglial cells undergo metabolic reprogramming in response to pathological stimuli, including Aβ plaques, Tau tangles, and α-synuclein aggregates. This metabolic shift is characterized by a transition from oxidative phosphorylation (OXPHOS) to glycolysis, increased glucose uptake, enhanced production of lactate, lipids, and succinate, and upregulation of glycolytic enzymes. These metabolic adaptations result in altered microglial functions, such as amplified inflammatory responses and diminished phagocytic capacity, which exacerbate neurodegeneration. This review highlights recent advances in understanding the molecular mechanisms underlying microglial metabolic reprogramming in neurodegenerative diseases and discusses potential therapeutic strategies targeting microglial metabolism to mitigate neuroinflammation and promote brain health. Microglial Metabolic Reprogramming in Neurodegenerative Diseases This graphical abstract illustrates the metabolic shift in microglial cells in response to pathological stimuli and highlights potential therapeutic strategies targeting microglial metabolism for improved brain health.
Insights
Microglia shift their metabolism from oxidative phosphorylation to glycolysis in neurodegenerative diseases. This metabolic reprogramming impairs their function, worsening brain conditions and inflammation.
Area of Science:
- Neuroimmunology
- Neurobiology
- Metabolic pathways
Background:
- Microglia are key immune cells in the central nervous system, crucial for brain homeostasis.
- Neurodegenerative diseases trigger metabolic changes in microglia, affecting their response to pathological stimuli like amyloid plaques and tau tangles.
Purpose of the Study:
- To review recent findings on the molecular mechanisms of microglial metabolic reprogramming in neurodegenerative diseases.
- To discuss therapeutic strategies targeting microglial metabolism for neuroinflammation and brain health.
Main Methods:
- Literature review of recent advances in neuroimmunology and metabolic research.
- Analysis of molecular mechanisms driving microglial metabolic shifts.
- Discussion of therapeutic targets for neurodegenerative conditions.
Main Results:
- Microglia transition from oxidative phosphorylation to glycolysis under pathological conditions.
- Increased glucose uptake, lactate, lipid, and succinate production are observed.
- Upregulation of glycolytic enzymes accompanies these metabolic adaptations.
Conclusions:
- Microglial metabolic reprogramming alters immune responses and phagocytic capacity, exacerbating neurodegeneration.
- Targeting microglial metabolism offers a promising therapeutic avenue for neurodegenerative diseases.
- Modulating microglial metabolic pathways could mitigate neuroinflammation and enhance brain health.
