Indoleamine 2,3-Dioxygenase as a Therapeutic Target for Alzheimer’s Disease and Geriatric Depression

Author:

Savonije Karl1,Meek Autumn1ORCID,Weaver Donald F.12

Affiliation:

1. Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada

2. Departments of Chemistry and Medicine, University of Toronto, Toronto, ON M5S 3M2, Canada

Abstract

Neuroimmune-triggered neuroinflammation of the central nervous system is emerging as an important aetiopathogenic factor for multiple neurological disorders, including depression, dementia, Alzheimer’s disease, multiple sclerosis and others. Tryptophan metabolism via the kynurenic pathway, which is initiated by the indoleamine-2,3-dioxygenase (IDO-1) enzyme, is a key regulator of the neuroimmune system and its associated neuroinflammatory effects. As discussed in this review, targeting the production of immunopathic and potentially neurotoxic kynurenine metabolites by inhibitory downregulation of IDO-1 may prove a viable target against inflammation-induced neurological conditions, particularly depression and dementia.

Funder

the Krembil Foundation, the Weston Foundation and a Harrington Scholar-Innovator Award

Publisher

MDPI AG

Subject

General Neuroscience

Reference84 articles.

1. Makowski, G.S. (2020). Advances in Clinical Chemistry, Elsevier.

2. Endogenous kynurenines as targets for drug discovery and development;Stone;Nat. Rev. Drug Discov.,2022

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5. IDO and regulatory T cells: A role for reverse signalling and non-canonical NF-kappaB activation;Puccetti;Nat. Rev. Immunol.,2007

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