Can kynurenine pathway be considered as a next-generation therapeutic target for Parkinson's disease? An update information

Biosci Trends. 2022 Sep 17;16(4):249-256. doi: 10.5582/bst.2022.01352. Epub 2022 Aug 24.

Abstract

By far, no revolutionary breakthrough in the treatment of Parkinson's disease (PD) was found. It is indeed a knotty problem to select a satisfactory strategy for treating some patients with advanced stage PD. Development of novel therapeutic targets against PD has been an urgent task faced by global PD researchers. Targets in the tryptophan-kynurenine pathway (KP) were then considered. Metabolites in the KP are liposoluble. Some neurotoxic metabolites, including 3-hydroxykynurenine and its downstream 3-hydroxyanthranilic acid and quinolinic acid, are mainly produced peripherally. They can easily cross the blood-brain barrier (BBB) and exert their neurotoxic effects in the central neuron system (CNS), which is considered as a potential pathophysiological mechanism of neurodegenerative diseases. Hence, agents against the targets in the KP have two characteristics: (1) being independent from the dopaminergic system and (2) being seldom affected by the BBB. Inspiringly, one agent, namely, the inhibitor of indoleamine 2,3-dioxygenase 1, has been currently reported to present satisfactory efficacy comparable to levodopa, implying that the KP might be a potential novel target for PD. This review collected and summarized the updated information regarding the association of the KP with PD, which is helpful for understanding the clinical value of the KP in the PD scenario.

Keywords: Blood-brain barrier; Dopaminergic medication; Indoleamine 2,3-dioxygenase 1 (IDO1); Parkinson's disease; Tryptophan-kynurenine pathway.

Publication types

  • Review

MeSH terms

  • 3-Hydroxyanthranilic Acid
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Kynurenine* / metabolism
  • Levodopa
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / metabolism
  • Quinolinic Acid / metabolism
  • Tryptophan / metabolism

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • 3-Hydroxyanthranilic Acid
  • Kynurenine
  • Levodopa
  • Tryptophan
  • Quinolinic Acid