Abstract
Immune-mediated activation of tryptophan (TRYP) catabolism via the 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 TRYP via the 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.
| Original language | English |
|---|---|
| Pages (from-to) | 39-42 |
| Number of pages | 4 |
| Journal | Neural Regeneration Research |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2017 |
| Externally published | Yes |
Bibliographical note
Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- kynurenine pathway
- tryptophan
- NAD+
- PARP
- Inflammation