Prompt Description

Parkinson’s disease is increasingly understood as a neurodegenerative disorder influenced not only by inherent neuronal susceptibility but also by pathological signaling within the neuroinflammatory microenvironment. In response to neurotoxic stress, microglia undergo sustained activation, marked by significant phosphorylation and nuclear translocation of Signal Transducer and Activator of Transcription 3 (STAT3). Activated STAT3 acts as a key transcriptional regulator, amplifying inflammatory signaling and modulating the microglial secretory profile. STAT3-activated microglia release soluble pro-inflammatory mediators into the extracellular environment, creating a neurotoxic conditioned medium that propagates inflammation via paracrine signaling. Exposure of dopaminergic neurons to this microglia-derived conditioned medium induces mitochondrial dysfunction, elevates oxidative stress, and activates apoptotic pathways, ultimately compromising neuronal survival and the dopaminergic phenotype.