Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis.
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'.
University of New South Wales, School of Medical Sciences, Dept. of Pharmacology, Sydney, Australia.
Jong-Min
JM
Lee
Macquarie University, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Sydney, Australia.
Vanessa
V
Tan
Macquarie University, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Sydney, Australia.
David
D
Lovejoy
University of New South Wales, School of Psychiatry, Sydney, Australia.
Nady
N
Braidy
Macquarie Neurology, Macquarie University, Sydney, Australia.
Dominic B
DB
Rowe
St Vincent's Hospital, Neurology Department, Sydney, Australia.
Bruce J
BJ
Brew
Macquarie University, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Sydney, Australia; Peter Duncan, Neurosciences Unit, St Vincent's Centre for Applied Medical Research, Sydney, Australia.
Gilles J
GJ
Guillemin
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000502:physiology; D017378:Quinolinic Acid / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid
Amyotrophic lateral sclerosis; Kynurenine pathway; Quinolinic acid; Therapeutic agents