NEUROINFLAMMATION AND NEURODEGENERATIVE DISEASES

Resumo

Summary: Neuroinflammati on is now understood as a central driver in the pathogenesis of neurodegenerative diseases, rather than a secondary response. It plays a key role in disorders such as Alzheimer’s, Parkinson’s, ALS, and Huntington’s disease, all marked by progressive neuron al loss and functional decline. The shift from an acute, protective inflammatory response to a chronic, neurotoxic state promotes disease progression through complex CNS signaling pathways. This review highlights that persistent activation of microglia and astrocytes into pro -inflammatory phenotypes sustains neuroinflammation. The NLRP3 inflammasome is a critical mediator, activated by protein aggregates like β -amyloid and α -synuclein, leading to Caspase -1 activation and increased production of pro-inflammatory cytokines (IL-1β and IL-18). This process enhances Tau hyperphosphorylation and plaque formation, reinforcing a harmful feedback loop. Additional factors, such as blood -brain barrier disruption and oxidative stress caused by reactive oxygen species an d nitric oxide, further contribute to neuronal damage. Emerging therapies, including drugs like dexmedetomidine and NLRP3 inhibitors, aim to restore glial cells to a neuroprotective state. Overall, targeting neuroinflammation -particularly inflammasome path ways and glial reprogramming-represents a promising strategy for developing disease -modifying treatments rather than merely alleviating symptoms.