Materials and metabolites of Kynureinine pathway in neurodegenerative diseases and multiple sclerosis

Kynurenine pathway (KP) plays an important role in the pathogenesis of neuroinflammation  and neurodegenerative disorders. The metabolites of this pathway can regulate neurotransmitters such as serotonin and melatonin, as well as regulates inflammatory pathways in central nervous system and peripheral nervous system. In neurodegenerative diseases (NDD) such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and Multiple sclerosis (MS), brain neurons are initially involved and gradually disappear. NDDs and MS are among the most debilitating and non-therapeutic diseases that are spreading rapidly in the world. In this review article, we will survey the role and effect of KP in the process of NDDs and MS. This study is a review article. Therefore, we have taken action by using the internal and external databases, to find and collect all research reports that have been conducted in recent years to evaluate the KP in NDDs and MS. Given the prevalence and importance of these diseases, there is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases. One of the molecular pathways with its metabolites that is common in all of the aforementioned diseases, is KP. The effect of KP is seen in many diseases, including NDDs and MS and in all of them, an imbalance in the level of tryptophan and its metabolites is observed. That is, if the amount of KP’s metabolites is returned to the normal range, it will reduce the symptoms of the disease, while the change in the balance of these metabolites seen in NDDs and MS will worsen and progress the disease. KP has been known as an important determinant of immune responses and tolerance in T cells. It seems that the destruction of tryptophan and the production of a number of downstream KP's metabolites, causes a disruption of protein synthesis, and the suppression of the production and proliferation of regulatory T cells (Treg), and this is in favor of incidence of disease such as MS.