Harnessing neuroinflammation for neuroregeneration

Neuroinflammation, traditionally perceived as a negative response in the central nervous system (CNS), is emerging as a complex phenomenon with both detrimental and regenerative capacities. This review explores the intricate interplay between neuroinflammation and neurodegeneration, with a special focus on its potential to drive neuroregeneration. Neuroinflammation is initiated by the activation of microglia and astrocytes, leading to the production of pro-inflammatory cytokines, chemokines and other mediators. While it can exacerbate neurodegenerative processes, recent insights reveal its dual nature, with certain conditions promoting neuronal repair and regeneration. We discuss the cellular mechanisms underlying neuroinflammation, including the activation of microglia, astrocyte reactivity and the infiltration of peripheral immune cells. The review also delves into the molecular mechanisms, highlighting the roles of toll-like receptors, nuclear factor-kappa B and inflammasomes in mediating neuroinflammatory responses. By examining neuroinflammation’s contribution to Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, we illustrate its critical role in neurodegeneration. Importantly, this review shifts focus to the regenerative potential of neuroinflammation. It investigates how the activation of microglia and astrocytes can assume a neuroprotective phenotype, releasing anti-inflammatory cytokines and growth factors that support neuronal survival and synaptic formation. We also explore therapeutic strategies that target neuroinflammation, including the use of anti-inflammatory drugs, lipopolysaccharides, interleukins and regulatory T cells. These strategies exemplify the potential to modulate neuroinflammation beneficially, thus opening avenues for novel neuroregenerative therapies. The review concludes by addressing the challenges and opportunities in harnessing neuroinflammation for therapeutic purposes, underscoring the need for a nuanced understanding of its role in the CNS.