Chapter

Targeting the Broadly Pathogenic Kynurenine Pathway

pp 205-213

Role of the Kynurenine Pathway in Epilepsy

  • Monika SharmaAffiliated withCarman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine
  • , Chaitali AnandAffiliated withTranslational Neuroscience Program, Children’s Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine
  • , Diane C. ChuganiAffiliated withCarman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Detroit Medical Center, Wayne State University School of MedicineDivision of Clinical Pharmacology and Toxicology, Children’s Hospital of Michigan, Wayne State University School of Medicine Email author 

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Abstract

A role for the kynurenine pathway (KP) of tryptophan (TRP) metabolism in epilepsy was first discovered when injections of the KP metabolite quinolinic acid (QA) in brain produced seizures in mice (Lapin IP. J Neural Transm. 42(1):37–43;1978). Subsequent studies have reported altered KP metabolites in animal models of epilepsy and in human epilepsy. Epilepsy is a complex group of disorders involving abnormal firing of neurons linked to an imbalance of excitatory and inhibitory mechanisms in the brain. KP metabolites act at several neurotransmitter receptors and can produce both excitatory and inhibitory effects. Thus, the role of the KP mechanisms in epilepsy, a condition characterized by an imbalance in excitation and inhibition, is important to consider. Furthermore, the KP is induced by inflammatory cytokines and is part of the inflammatory response increasingly recognized to play a role in epilepsy and epileptogenesis (Vezzani A. Epilepsy Curr. 14(1 Suppl):3–7;2014). In this chapter, we discuss evidence for the role of the KP in the balance of excitation and inhibition and the inflammatory process in animal models, as well as evidence for a role of kynurenines in human epilepsy. Finally, therapeutic targets for epilepsy in the KP are discussed.

Keywords

Epilepsy Kynurenine Tryptophan Inflammation α-[11C]methyl-l-tryptophan