Inflammation, Dopaminergic Brain and Bilirubin

Dopamine is a well-known neurotransmitter due to its involvement in Parkinson's disease (PD). Dopamine is not only involved in PD but also controls multiple mental and physical activities, such as the pleasure of food, friends and loved ones, music, art, mood, cognition, motivation, fear, affective disorders, addiction, attention deficit disorder, depression, and schizophrenia. Dopaminergic neurons (DOPAn) are susceptible to stressors, and inflammation is a recognized risk for neuronal malfunctioning and cell death in major neurodegenerative diseases. Less is known for non-neurodegenerative conditions. Among the endogenous defenses, bilirubin, a heme metabolite, has been shown to possess important anti-inflammatory activity and, most importantly, to prevent DOPAn demise in an ex vivo model of PD by acting on the tumor necrosis factor-alpha (TNFa). This review summarizes the evidence linking DOPAn, inflammation (when possible, specifically TNFa), and bilirubin as an anti-inflammatory in order to understand what is known, the gaps that need filling, and the hypotheses of anti-inflammatory strategies to preserve dopamine homeostasis with bilirubin included.

Automated summary

Dopamine, a well-known neurotransmitter, plays a crucial role in Parkinson's disease and various mental and physical activities. Inflammation is recognized as a risk factor for neuronal malfunctioning and cell death in neurodegenerative diseases. Bilirubin, an endogenous defense, has been found to possess anti-inflammatory activity and prevent dopamine neuron demise. This review aims to understand the links between dopamine, inflammation (specifically TNFa), and bilirubin as an anti-inflammatory and explore strategies to preserve dopamine homeostasis.