Role of Kynurenine and Its Derivatives in the Neuroimmune System

Int J Mol Sci. 2024 Jun 28;25(13):7144. doi: 10.3390/ijms25137144.

Abstract

In recent years, there has been a growing realization of intricate interactions between the nervous and immune systems, characterized by shared humoral factors and receptors. This interplay forms the basis of the neuroimmune system, the understanding of which will provide insights into the pathogenesis of neurological diseases, in which the involvement of the immune system has been overlooked. Kynurenine and its derivatives derived from tryptophan have long been implicated in the pathogenesis of various neurological diseases. Recent studies have revealed their close association not only with neurological disorders but also with sepsis-related deaths. This review provides an overview of the biochemistry of kynurenine and its derivatives, followed by a discussion of their role via the modulation of the neuroimmune system in various diseases.

Keywords: brain; kynurenine pathway; neuroimmunology; sepsis; tryptophan.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune System / immunology
  • Immune System / metabolism
  • Kynurenine* / metabolism
  • Nervous System Diseases / immunology
  • Nervous System Diseases / metabolism
  • Neuroimmunomodulation*
  • Sepsis / immunology
  • Sepsis / metabolism
  • Tryptophan / chemistry
  • Tryptophan / metabolism

Substances

  • Kynurenine
  • Tryptophan

Grants and funding

This research was funded by a grant from KAKENHI (JP21H03114, JP16K15665, JP18H02970, JP16K15665, JP19K22712, JP23K17376 to K.M.), P-PROMOTE from Japan Agency for Medical Research and Development (to K.M.), Takeda Science Foundation (to K.M.), Lotte Foundation (to K.M.), Kowa Life Science Foundation (to K.M.), Kanzawa Medical Research Foundation (to K.M.), Akashi Medical Foundation (to K.M.), Yakult Bioscience Research Foundation (to K.M.), Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care (to K.M.), Japan Dairy Association (to K.M.), Lydia O’Leary Memorial Pias Dermatological Foundation (to K.M.), Canon Foundation (to K.M.), Japan Intractable Diseases Research Foundation (to K.M.), Uehara Memorial Foundation (to K.M.), Terumo Life Science Foundation (to K.M.), Inoue Foundation for Science (to K.M.), Brain Science Foundation (to K.M.), Nakajima Foundation (to K.M.), Life Science Foundation (to K.M.), Mitsubishi Foundation (to K.M.), Astellas Foundation (to K.M.), Gushinkai Foundation (to K.M.), Okamoto Research Award (to K.M.), Asahi Glass Foundation (to K.M.), Senri Life Science Foundation (to K.M.), Inamori Foundation (to K.M.), Daiichi Sankyo Foundation (to K.M.), Sumitomo Foundation (to K.M.), Princess Takamatsu Cancer Research Fund (to K.M.), Relay for Life Japna Project Future (to K.M.), SGH Foundation (to K.M.), Kato Memorial Bioscience Foundation (to K.M.), Waksman Foundation (to K.M.), Astellas Foundation for Research on Metabolic Disorders (to K.M.), Mochida Memorial Foundation for Medical and Pharmaceutical Research (to K.M.), Naito Foundation (to K.M.), Foundation for Promotion of Cancer Research (to K.M.) and Toyoaki Scholarship Foundation (to K.M).