Immune cell dynamics in neurological disorders: from inflammation to microgliopathy and Neuron-Glia crosstalk.

The immune system is a complex network of cells and molecules that preserves homeostasis and provides defence against pathogens. Within the central nervous system (CNS), immune cells perform distinct yet integrated roles, balancing neuronal survival with inflammatory responses. Neuroinflammation is a hallmark of several neurological disorders, where immune activation may become maladaptive and drive neurodegeneration. Microglia, the resident macrophage-like immune cells of the brain, represent a unique interface between immune and neural function. They regulate synaptic pruning, release trophic factors, and respond to injury; however, their chronic or patchy activation leads to microgliopathy, an emerging pathological state underpinning diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and ischemic stroke. This review traces the evolution of immune involvement from peripheral to central contexts, examines microglial signalling mechanisms in health and disease, and highlights how dysregulated neuron–microglia communication contributes to disease pathology. This review also explores biomarkers, signalling cascades such as NF-κB, MAPK, JAK/STAT, and calcium-mediated pathways, and discuss future perspectives on targeting microglial states for therapeutic intervention.