Emerging therapeutic approaches targeting neuroinflammation in neurodegenerative diseases

Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies, still pose a serious challenge to global public health due to the non-availability of disease-modifying therapeutic modalities. Emerging evidence shows the important role of neuroinflammation in contributing to disease progression, driven by the activation of glial cells (microglia and astrocytes) and cytokine dysfunction. The functional polarization of microglia and astrocytes is critical to disease mechanisms. Pro- inflammatory M1 microglia and A1 astrocytes contribute to neurotoxic mediator production and M2 and A2 polarize towards repair mechanisms andrestore neuronal homeostasis. Recent breakthroughs in translational medicine have been geared towards exploiting inflammatory pathways with the help of kinase inhibitors, cytokine modulators, and biologicals to attain neuroimmune homeostasis. This review reports the intricacies of neuronal inflammation pathways and current trial-based therapeutic modalities, with attention focused on Phase 1-3 trials of potential therapeutic candidates. These mechanism-based and biomarker-guided approaches are shaping a new generation of precision therapies that hold promise for slowing or preventing neurodegeneration.