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Role of the Kynurenine Pathway in Stem Cell Biology

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Targeting the Broadly Pathogenic Kynurenine Pathway

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Abstract

The KYN pathway (KP) is the main catabolic pathway of the essential amino acid TRP. The KP has been identified as playing critical roles in the regulation of the immune response in a variety of experimental settings. It is also known to be involved in several neuroinflammatory diseases including Huntington’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease. This chapter considers the current understanding of the role of the KP in stem cell biology. Both these fundamental areas of cell biology have independently been the focus of a burgeoning research interest in recent years. However, little is known about how these two important fields of research interact. Several of the inflammatory and infectious diseases in which the KP has been implicated include those for which stem cell therapies are being actively explored at a clinical level. Therefore, it is highly pertinent to consider the evidence that the KP influences stem cell biology and impacts on the functional behaviour of progenitor cells.

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Abbreviations

1-MT:

1-Methyl tryptophan

3-HAA:

3-Hydroxyanthranilic acid

AhR:

Aryl hydrocarbon receptor

CNS:

Central nervous system

EAE:

Experimental autoimmune encephalomyelitis

ESC:

Embryonic stem cell

FASD:

Fetal alcohol spectrum disorders

hESC:

Human embryonic stem cells

HSC:

Haematopoietic stem cell

IDO:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon-γ

KMO:

Kynurenine 3-monooxygenase

KP:

Kynurenine pathway

KYNA:

Kynurenic acid

MSC:

Mesenchymal stem cell

NAD+:

Nicotinamide adenine dinucleotide

NMDA:

N-methyl-d-aspartate

NSC:

Neural stem cell

PGE2:

Prostaglandin E2

PIC:

Picolinic acid

QUIN:

Quinolinic acid

TDO:

Tryptophan 2,3-dioxygenase

TGF-β1:

Transforming growth factor-β1

TRP:

Tryptophan

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Acknowledgements

This work was supported by the Multiple Sclerosis Research Association (MSRA) and the University of New South Wales, Australia.

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Authors and Affiliations

  1. Applied Neurosciences, St. Vincent’s Centre for Applied Medical Research, University of New South Wales, Level 8, Lowy-Packer Building, 405 Liverpool Street, Darlinghurst, NSW, Australia

    Simon P. Jones M.Sc., Ph.D., P.G.C.E., Gilles J. Guillemin & Bruce J. Brew

  2. Australian School of Advanced Medicine, Macquarie University, Sydney, Australia

    Gilles J. Guillemin

  3. Department of Neurology, St Vincent’s Hospital, Sydney, Australia

    Bruce J. Brew

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  1. Simon P. Jones M.Sc., Ph.D., P.G.C.E.
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  2. Gilles J. Guillemin
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  3. Bruce J. Brew
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Correspondence to Simon P. Jones M.Sc., Ph.D., P.G.C.E. .

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Jones, S.P., Guillemin, G.J., Brew, B.J. (2015). Role of the Kynurenine Pathway in Stem Cell Biology. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_20

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