The Involvement of Kynurenine Pathway in Neurodegenerative Diseases

Background: A growing body of evidence has shown the involvement of the kynurenine pathway (KP), the primary route of tryptophan (TRP) catabolism, in the pathophysiology of neuropsychiatric disorders. Objective: The study aims to provide a comprehensive and critical overview of the clinical evidence on the KP involvement in the pathophysiology of Alzheimer’s disease (AD) and Parkinson's disease (PD), discussing therapeutic opportunities. Methods: We searched for studies investigating KP metabolites in human subjects with AD and/or PD. Results: Postmortem studies showed altered levels of KP metabolites in the brain of AD and PD patients compared with controls. Cross-sectional studies have reported associations between peripheral levels (serum or plasma) of KP metabolites and cognitive function in these patients, but the results are not always concordant. Conclusion: Given the emerging evidence of the involvement of KP in the pathophysiology of neuropsychiatric/neurodegenerative diseases and promising results from preclinical pharmacological studies, a better understanding of the KP involvement in AD and PD is warranted. Future longitudinal studies are needed to define the direction of the observed associations and specific therapeutic targets within the KP.