Decoding Microglial Polarization and Metabolic Reprogramming in Neurodegenerative Diseases: Implications for Disease Progression and Therapy.

As the resident macrophages of the brain, microglia are crucial immune cells specific to the central nervous system (CNS). They constantly surveil their surroundings and trigger immunological reactions, playing a key role in various neurodegenerative diseases (ND). As illnesses progress, microglia exhibit multiple phenotypes. Traditionally, microglia have been classified into two main phenotypes upon activation: the pro-inflammatory M1 polarization and the anti-inflammatory M2 polarization. However, this classification is now considered overly simplistic, as it is unable to fully convey the intricacy and diversity of the inflammatory response. Immune regulatory factors, such as chemokines secreted by microglia, are essential for modulating brain development, maintaining the neural milieu, and orchestrating responses to injury, along with the subsequent repair processes. However, in recent years, the significance of metabolic reprogramming in both physiological microglial activity and ND has also become increasingly recognized. Upon activation-triggered by brain injury, infection, or ND-microglia typically modify their metabolic processes by transitioning from oxidative phosphorylation (OXPHOS) phosphorylation to glycolysis. This shift facilitates rapid energy production but may also enhance pro-inflammatory responses. This review seeks to summarize metabolic reprogramming and polarization in the function of microglia and their involvement in ND.