title: Kynurenine pathway metabolism and neuroinflammatory disease.
abstract: Immune-mediated activation of tryptophan (TRYP) catabolismviathe kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYPviathe KP during an immune response. Under physiological conditions, QUIN is metabolized to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), which represents an important metabolic cofactor and electron transporter. NAD+also serves as a substrate for the DNA 'nick sensor' and putative nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP). Free radical initiated DNA damage, PARP activation and NAD+depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Faculty of Medicine, Sydney, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: School of Medical Sciences, University of New South Wales, Faculty of Medicine, Sydney, Australia; Australasian Research Institute, Sydney Adventist Hospital, Sydney, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Grant
keywords: NAD+; PARP; inflammation; kynurenine pathway; tryptophan