Prompt Description

In response to pathological stimuli such as MPP+, activated microglia undergo STAT3 phosphorylation and nuclear translocation, leading to transcriptional upregulation and the subsequent release of pro-inflammatory mediators, including TNF-α, IL-1β, and IL-6. Paracrine signaling resulting from exposure of dopaminergic neurons to this microglia-derived conditioned medium induces mitochondrial dysfunction and exacerbates oxidative stress through the accumulation of reactive oxygen species, ultimately reducing neuronal survival. Treatment with the STAT3 inhibitor B35t effectively suppresses microglial STAT3 activation and nuclear translocation, thereby reducing the secretion of neurotoxic inflammatory factors. Consequently, this pharmacological intervention attenuates paracrine neurotoxicity, preserves mitochondrial integrity within dopaminergic neurons, and maintains neuronal viability, establishing the microglial STAT3 axis as a critical functional pathway in neurodegeneration.