Microglial phagocytosis

Microglial phagocytosis is the primary biological process by which microglia, the resident immune cells of the central nervous system (CNS), identify, engulf, and degrade cellular debris, pathogens, and protein aggregates. This mechanism is essential for maintaining CNS homeostasis, facilitating neurodevelopment through synaptic pruning, and preventing the accumulation of neurotoxic materials. Although it is a cellular process rather than a single molecular target, it is a major focus of drug discovery for neurodegenerative diseases where phagocytic efficiency is often impaired. Therapeutic efforts aim to modulate this process by targeting specific molecular regulators such as TREM2, CD33, and the complement system. Enhancing microglial phagocytosis is hypothesized to slow disease progression in conditions like Alzheimer's and Multiple Sclerosis by clearing amyloid-beta plaques or myelin debris. However, therapeutic challenges include the risk of inducing excessive synaptic loss or triggering hyper-inflammatory responses that could exacerbate neurodegeneration.

Other names

CNS phagocytosisMicroglial clearanceEfferocytosisMicroglial engulfmentSynaptic pruning

Therapeutic strategies modulate microglial phagocytosis by targeting regulatory surface receptors (e.g., TREM2 agonism, CD33 antagonism) or complement proteins (e.g., C1q inhibition) to enhance the engulfment and lysosomal degradation of pathological aggregates like amyloid-beta, myelin debris, and apoptotic neurons.