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Bilirubin and inflammation in neurodegenerative and other neurological diseases

Inflammation links neurodegenerative, neuropsychiatric and other neurological diseases (NDs) with acute brain events. It is responsible for the alteration of neurotransmission and circuity, brain architecture, and cell fate, affecting mood and personality (anxiety, depression and schizophrenia) and behavior (decline in cognitive, motor and speech abilities, altered sleep, fatigue, pain sensitivity and dementia). Inflammation is also a key component in systemic chronic diseases (cardiovascular disease, cancer, diabetes, and metabolic syndrome), in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule, and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started. While altered serum bilirubin levels have been reported in ND patients, the potential activity of bilirubin in the brain is vague. This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation, aiming to elucidate the pigment’s role in the central nervous system environment.