The Role of Mast Cells and Their Potential as a Therapeutic Target For Neuroinflammation

Neuroinflammation is increasingly recognized as a central mechanism underlying the onset and progression of numerous neurological disorders, including neurodegenerative, autoimmune, and cerebrovascular diseases. Although microglia and astrocytes are traditionally considered the primary mediators of inflammatory responses within the central nervous system (CNS), accumulating evidence has identified mast cells (MCs) as important contributors to neuroimmune regulation. Strategically located at the interface between the peripheral immune system and the CNS, MCs can rapidly respond to a variety of endogenous and exogenous stimuli through the release of bioactive mediators, including histamine, proteases, cytokines, chemokines, and lipid-derived molecules. These mediators influence blood-brain barrier (BBB) integrity, promote glial activation, modulate neuronal signaling, and contribute to the amplification of inflammatory cascades. Increasing experimental and clinical evidence supports the involvement of MCs in the pathogenesis of several neurological conditions, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, migraine, and ischemic brain injury. Consequently, modulation of mast cell activity has emerged as a promising therapeutic approach for limiting neuroinflammatory damage and restoring neuroimmune homeostasis. This review provides an overview of mast cell biology within the CNS, discusses the molecular mechanisms linking MCs to neuroinflammation, examines their contribution to major neurological disorders, and highlights current and emerging therapeutic strategies targeting MCs-mediated pathways. A deeper understanding of mast cell functions in neuroinflammatory processes may facilitate the development of innovative and more effective interventions for neurological diseases.