Abstract

Background & aim: Kynurenine pathway (KP) plays an important role in the pathogenesis of neuroinflammation and neurodegenerative disorders. In neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and several autoimmune diseases such as Multiple sclerosis (MS), brain neurons are initially involved and gradually destroyed. In the present review article, the role and effect of changes in the balance of KP metabolites in the exacerbation of neurodegenerative disorders will be discussed

Methods: In the present review, we conducted a comprehensive searching method in various online databases including MEDLINE, Scopus, Embase, and Google Scholar to collect all research studies that have been done in recent years to study and evaluate KP and its metabolites in neurodegenerative diseases and MS

Results:Regarding the prevalence and importance of these diseases, there is an urgent need to develop new and more effective therapeutic strategies to fight these destructive diseases. One of the molecular pathways involved in all these diseases is the KP, which the effects of its metabolites are observed in many diseases, including neurodegeneration process. In all of these diseases, an imbalance in the levels of tryptophan and its metabolites has been observed. Animal studies have shown that if the levels of neurotoxic and neuroprotective metabolites of the pathway return to the normal range, the symptoms of the disease will decrease or the disease process will be slowed down. While disturbing this balance leads to disease progression and worsening of symptoms.

Conclusion: The KP is an important determinant of immune responses and tolerance in T cells. In such conditions, it seems that by increasing the degradation of tryptophan and the production and accumulation of a large number of downstream neurotoxic metabolites, disruption of protein synthesis and suppression of the production and proliferation of regulatory T cells (Tregs) occurs, which leads to the development of neurodegeneration process