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Review
. 2023 May 24;13(6):852.
doi: 10.3390/brainsci13060852.

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

Karl Savonije  1 , Autumn Meek  1 , Donald F Weaver  1   2
Affiliations
Review

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

Karl Savonije et al. Brain Sci. .

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.

Keywords: Alzheimer’s disease; dementia; depression; indoleamine 2,3-dioxygenase; neuroinflammation; tryptophan.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kynurenic metabolic pathway of tryptophan.
Figure 2
Figure 2
Molecular modeling optimized structure of IDO-1.
Figure 3
Figure 3
Structures of known IDO inhibitors developed for oncology indications.
Figure 3
Figure 3
Structures of known IDO inhibitors developed for oncology indications.
Figure 4
Figure 4
General structure of proposed brain-penetrant IDO inhibitors.
See this image and copyright information in PMC

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