Abstract:Parkinson’s disease (PD) is a progressive neurodegenerative disorder classically characterized by motor symptoms. However, its non-motor symptoms, particularly depression, significantly impact patients’ quality of life and often precede the onset of motor symptoms. In recent years, the role of neuroimmune inflammation in the pathogenesis of PD and its associated depressive symptoms has garnered increasing attention. This article systematically reviews the characteristics of the neuroinflammatory microenvironment in the context of PD, with a focus on the interplay between microglial activation, mitochondrial dysfunction, and dopaminergic neuron damage. Based on this, this article analyzes the potential value of the G protein coupled receptor 109A (GPR109A) receptor, a key molecule linking metabolism and immunity, in regulating neuroinflammation and its prospects for PD therapy. Finally, considering the anatomical basis of the medial prefrontal cortex in the pathogenesis of depression, this article proposes the hypothesis that GPR109A agonists may alleviate depressive symptoms in PD by ameliorating neuroinflammation, thereby offering new insights for future research.