SELECTIVE INHIBITION OF HDAC6 MODULATES MICROGLIAL POLARIZATION AND ATTENUATES NEUROINFLAMMATION IN AN LPS-INDUCED NEURODEGENERATIVE MOUSE MODEL

Neuroinflammation, which is primarily brought on by the ongoing overactivation of microglia, is a key feature in the pathogenesis of many neurodegenerative diseases. Due to their functional plasticity, these immune cells that dwell in the central nervous system can alternate between a pro-inflammatory (M1) phenotype that exacerbates neuronal damage and an anti-inflammatory (M2) phenotype that promotes tissue repair and neuroprotection. This study aimed to evaluate the degree to which particular inhibitors of Histone Deacetylase 6 (HDAC6) could modify this microglial polarisation. To track phenotypic changes, BV-2 microglial cells exposed with lipopolysaccharide (LPS) to simulate an inflammatory milieu were administered selective inhibitors, such as tubastatin A. The subsequent Western Blot and PCR analysis of pro-inflammatory cytokines and particular M1/M2 markers showed that HDAC6 inhibition greatly reduced the production of reactive oxygen species (ROS) and the expression of M1 indicators. M2-associated markers showed a strong increase at the same time, suggesting a successful shift to a neuroprotective state. These findings imply that specific HDAC6 inhibitors serve as essential "molecular switches" that can alter the brain's immunological response. These inhibitors provide a unique and highly targeted therapeutic approach for the treatment of neurodegenerative illnesses by reducing neuroinflammation and promoting a reparative cellular milieu, ultimately offering a method to maintain neuronal integrity and halt the course of the disease.