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The Kynurenine Pathway at the Interface Between Neuroinflammation, Oxidative Stress, and Neurochemical Disturbances: Emphasis in Schizophrenia

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Abstract

In recent years, the correlation between the kynurenine pathway (KP) metabolism, immune system activation, oxidative damage, and disorders of the CNS has been intensively explored. Recently, it has been postulated that KP could play a major role in both brain physiology and pathology, and this is due to the fact that this metabolic pathway contains at least two well-characterized neuroactive metabolites: quinolinic acid and kynurenic acid (KYNA). Other metabolites from the same pathway have shown to possess pro- and antioxidant properties. Moreover, KP includes enzymes that are modulated by inflammatory factors and free radicals. Altogether, this evidence suggests that KP metabolites could actively participate in a wide range of physiological and pathological events (Carpenedo et al., Eur J Neurosci 13:2141–2147, 2001; Leipnitz et al., Neurochem Int 50:83–94, 2007; Rassoulpour et al., J Neurochem 93:762–765, 2005; Schwarcz et al. 2010). Therefore, a cerebral unbalance oriented to generate some of these metabolites directly impacts on glutamatergic, dopaminergic, and cholinergic transmissions and is often associated with neurological, neurodegenerative, and psychiatric disorders, such as schizophrenia, which is known to be a cognitive decline associated with altered levels of KYNA, one of the recently recognized metabolic targets to handle this disorder.

Rafael Lugo-Huitrón: Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México. CONACyT scholarship holder 262378

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Abbreviations

3-HANA:

3-hydroxyanthranilic acid

3‑HAO:

3-hydroxyanthranilic acid 3, 4-dioxygenase

3-HK:

3-hydroxykynurenine

ABTS:

2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)

BBB:

Blood brain barrier

CNS:

Central nervous system

DA:

Dopamine

GABA:

Gamma-aminobutyric acid

Glu:

Glutamate

H2O2 :

Hydrogen peroxide

HO-1:

Heme oxygenase-1

IDO:

Indoleamine 2,3-dioxygenase

KATs:

Kynurenine aminotransferases

KMO:

Kynurenine 3-monooxygenase

KP:

Kynurenine pathway

KYN:

Kynurenine

KYNA:

Kynurenic acid

LDL:

Low-density lipoprotein

MAPKs:

Mitogen-activated protein kinases

NF-κB:

Factor nuclear factor-kappa B

NOS:

Nitric oxide synthase

PFC:

Prefrontal cortex

QUIN:

Quinolinic acid

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SP:

Schizophrenia

TDO:

Tryptophan 2,3-dioxygenase

Trp:

Tryptophan

XA:

Xanthurenic acid

α7nAChR:

α7 nicotine acetylcholine receptor

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Authors and Affiliations

  1. Laboratorio de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A., Mexico D.F., 14269, Mexico

    Benjamín Pineda Ph.D.

  2. Laboratory of Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery, Mexico City, Mexico

    Victoria Campos-Peña Ph.D.

  3. Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Mexico City, 14269, Mexico

    Rafael Lugo-Huitrón M.Sc. & Camilo Ríos Ph.D.

  4. Department of Neurochemistry, National Institute of Neurology and Neurosurgery, Mexico City, 14269, Mexico

    Verónica Pérez-de la Cruz Ph.D.

  5. Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico D.F., 14269, Mexico

    Verónica Pérez-de la Cruz Ph.D.

Authors
  1. Benjamín Pineda Ph.D.
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  2. Victoria Campos-Peña Ph.D.
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  3. Rafael Lugo-Huitrón M.Sc.
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  4. Camilo Ríos Ph.D.
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  5. Verónica Pérez-de la Cruz Ph.D.
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Correspondence to Verónica Pérez-de la Cruz Ph.D. .

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  1. Department of Biological Psychiatry of the Chair of Experimental and Clinical Physiology, Medical University of Lodz, Lodz, Poland

    Anna Dietrich-Muszalska

  2. Department of Neurochemistry, New York State Institute for Basic Research, Staten Island, New York, USA

    Ved Chauhan

  3. Departments of Psychiatry and Physiology & Biophysics, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Sylvain Grignon

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Pineda, B., Campos-Peña, V., Lugo-Huitrón, R., Ríos, C., Pérez-de la Cruz, V. (2015). The Kynurenine Pathway at the Interface Between Neuroinflammation, Oxidative Stress, and Neurochemical Disturbances: Emphasis in Schizophrenia. In: Dietrich-Muszalska, A., Chauhan, V., Grignon, S. (eds) Studies on Psychiatric Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0440-2_13

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