Fig. 1.

NIE modulatory network in PD: a confluence of neuroinflammation and neuroendocrine systems. The neuroinflammation and neuroendocrine systems recapitulate the pathophysiologic processes of PD. Specifically, the former is a convergent point for pro-inflammatory genetic factors, environmental toxin-induced inflammation, DA depletion, and SNCA accumulation, which collectively contribute to the neuroinflammatory events in the pathogenesis of PD. In contrast, the hypothalamic dopaminergic network dysfunction, circadian rhythm disorder, and brain–gut axis-mediated pathological dissemination execute as the neuroendocrine nodes to incorporate the neural and endocrine systems into a symptomatic entity in PD, with DA and melatonin as the connectors of the NIE modulatory network