Neuroinflammation across the Spectrum of Neurodegenerative Diseases: Mechanisms and Therapeutic Frontiers

BACKGROUND: Neuroinflammation is a central and dynamic driver in the pathophysiology of multiple neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Rather than being a mere consequence of neuronal injury, inflammatory processes, mediated by microglia, astrocytes, peripheral immune cells, and a range of molecular mediators, actively influence disease onset, progression, and clinical manifestations. SUMMARY: This review aims to synthesize current insights into the cellular and molecular mechanisms that orchestrate neuroinflammatory responses, emphasizing both convergent and disease-specific pathways. It examines the interaction between innate and adaptive immunity in shaping neuronal vulnerability, as well as the bidirectional communication between systemic and central immune systems. Special emphasis is placed on emerging therapeutic strategies, such as immunomodulatory drugs, glial-targeted interventions, and innovative delivery platforms. The discussion integrates findings from diverse disease models and disciplines to identify translational challenges and potential paths toward precision neuroimmunology. KEY MESSAGES: The impact of neuroinflammation arises from a complex interaction of shared and disease-specific immune pathways, with both innate and adaptive mechanisms shaping neuronal vulnerability. The crosstalk between peripheral and central immune compartments further modulates disease course, underscoring the importance of understanding these interactions in therapeutic design. While emerging strategies targeting neuroinflammation, including immunomodulatory drugs, glial-focused interventions, and novel delivery platforms, hold considerable promise, their translation into clinical benefit requires overcoming challenges in specificity, safety, and delivery. Ultimately, integrating multidisciplinary insights into immune-brain communication will be critical to advancing precision medicine approaches for neurodegenerative disorders.