Microglial metabolic reprogramming in Alzheimer's disease: Pathways, mechanisms, and therapeutic implications

Area of Science:

• Neuroscience
• Immunology
• Metabolism

Background:

• Microglia (MG) are the primary immune cells in the central nervous system.
• Microglial metabolism is increasingly recognized for its role in neurodegenerative diseases like Alzheimer's disease (AD).
• Metabolic reprogramming in microglia influences AD onset and progression.

Purpose of the Study:

• To comprehensively review microglial metabolic reprogramming in Alzheimer's disease.
• To explore the role of key energy substrates (glucose, fatty acids, amino acids) and signaling pathways in microglial metabolism.
• To discuss the potential of metabolomics for early AD diagnosis and novel therapeutic strategies targeting microglial function.

Main Methods:

• Literature review focusing on microglial metabolism in Alzheimer's disease.
• Analysis of signaling pathways regulating microglial metabolic reprogramming (e.g., TREM2, PI3K-AKT-mTOR, HIF-1α, AMPK, PPARs, LXRs).
• Exploration of metabolomics applications and therapeutic targets for AD.

Main Results:

• Metabolic reprogramming of microglia, involving glucose, fatty acid, and amino acid pathways, is central to AD pathogenesis.
• Specific molecular signaling pathways critically regulate these metabolic shifts in microglia.
• Metabolomics shows promise for early AD detection, and therapeutic interventions targeting microglial metabolism could mitigate disease progression.

Conclusions:

• Microglial metabolic reprogramming is intricately linked to the Alzheimer's disease cascade.
• Targeting microglial metabolism presents a promising strategy for developing novel AD therapeutics.
• Further research into the dynamic network of microglial metabolic reprogramming can inform innovative drug development for neuroprotection.