Activity studies of indoleamine 2,3-dioxygenase 1 enzyme

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Immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) plays a pivotal role in regulating the metabolism of L-tryptophan (L-Trp) through kynurenine pathway, which is a well-established therapeutic target for the treatment of diseases associated with immunosuppression. Under pathophysiological conditions the expression of IDO1 enzyme from its mRNA gets highly up-regulated in response to inflammatory signals (like interferon-γ) within the immune system. Up-regulation of the IDO1 enzyme is directly related with several diseases including cancer, neurodegenerative disorders (Alzheimer’s disease), Huntington’s disease, schizophrenia, depression, age-related cataract, and HIV-1 encephalitis. Hence, proper understanding of the IDO1 activity will be helpful for the development of novel IDO1 inhibitors as emerging immuno-oncology agents.On the basis of the experimental works performed during the research period, the content of the thesis entitled “Activity Studies of Indoleamine 2,3-Dioxygenase 1 Enzyme” have been divided into five chapters. Chapter 1 of the thesis provides an overview of IDO1 enzyme and demonstrates the activity and regulation of this immunosuppressive enzyme in medicine, life science and other related research fields. These enzymes are responsible for the degradation of an essential amino acid L-Trp, which is required for the protein synthesis and other important metabolic functions. IDO1 mediated depletion of the local L-Trp concentration and accumulation of the kynurenine metabolites regulate the local immunosuppression.
Supervisor: Debasis Manna