Chronic neuroinflammation is no longer viewed merely as a secondary consequence of neurodegeneration, but as a primary, dynamic driver of disease progression. In pathologies such as Alzheimer’s, Parkinson’s, and Amyotrophic Lateral Sclerosis, the sustained activation of microglia and astrocytes, coupled with blood-brain barrier dysfunction and systemic immune crosstalk, perpetuates a neurotoxic microenvironment that accelerates structural damage.

This Special Issue of Advanced Neurology aims to unite cutting-edge research illuminating the dual neuroprotective and neurodestructive roles of the central nervous system's immune response. We seek original research and comprehensive reviews spanning high-resolution spatial multi-omics, novel fluid and PET biomarkers, advanced computational modelling of glial phenotypes, and translational therapeutic strategies targeting inflammatory pathways. By bridging basic mechanistic insights with clinical reality, this volume serves as a platform for the next generation of disease-modifying interventions.