Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by a progressive degeneration of central and peripheral motor neurons, leading to the atrophy of voluntary muscles. It has been previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in ALS. In particular, the neuroactive intermediate, quinolinic acid (QUIN) has been shown to accumulate with a concomitant decrease in other neuroprotective and immunomodulatory KP metabolites. Furthermore, multiple biochemical phenomena associated with QUIN cytotoxicity are present in ALS, suggesting that QUIN may play a substantial role in the pathogenesis of ALS. This review highlights the potential roles of QUIN in ALS, and explores KP modulation as a therapeutic candidate in ALS. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

Keywords: Amyotrophic lateral sclerosis; Kynurenine pathway; Quinolinic acid; Therapeutic agents.