TY - JOUR
T1 - Quinolinic acid in the pathogenesis of Alzheimer's disease
AU - Guillemin, Gilles J.
AU - Williams, Kieran R.
AU - Smith, Danielle G.
AU - Smythe, George A.
AU - Croitoru-Lamoury, Juliana
AU - Brew, Bruce J.
PY - 2003
Y1 - 2003
N2 - We propose that the tryptophan catabolites produced through the kynurenine pathway (KP), and more particularly quinolinic acid (QUIN), may play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we demonstrated that after 72 hours amyloid peptide (Aβ) 1-42 induced indoleamine 2,3-dioxygenase (IDO) expression and in a significant increase in production of QUIN by human macrophages and microglia. In contrast, Aβ11-40 and Prion peptide (PrP) 106-126 did not induce any significant increase in QUIN production. We also investigated the potential modulatory effect of QUIN and kynurenic acid (KYNA) on Aβ11-42 and Aβ1-40 aggregation. After 24 and 120 hours, we did not observe any significant difference in the level of aggregation compared to the control (Aβ alone). Aβ has been shown to induce IL1-β mRNA expression by human foetal astrocytes and macrophages. We demonstrate that QUIN has the same effect. Interestingly, IL-Iβ has been found in association with plaques in AD. All together these data imply that QUIN may be, locally, one of the factors involved in the pathogenesis of neuronal damage in AD.
AB - We propose that the tryptophan catabolites produced through the kynurenine pathway (KP), and more particularly quinolinic acid (QUIN), may play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we demonstrated that after 72 hours amyloid peptide (Aβ) 1-42 induced indoleamine 2,3-dioxygenase (IDO) expression and in a significant increase in production of QUIN by human macrophages and microglia. In contrast, Aβ11-40 and Prion peptide (PrP) 106-126 did not induce any significant increase in QUIN production. We also investigated the potential modulatory effect of QUIN and kynurenic acid (KYNA) on Aβ11-42 and Aβ1-40 aggregation. After 24 and 120 hours, we did not observe any significant difference in the level of aggregation compared to the control (Aβ alone). Aβ has been shown to induce IL1-β mRNA expression by human foetal astrocytes and macrophages. We demonstrate that QUIN has the same effect. Interestingly, IL-Iβ has been found in association with plaques in AD. All together these data imply that QUIN may be, locally, one of the factors involved in the pathogenesis of neuronal damage in AD.
UR - http://www.scopus.com/inward/record.url?scp=1042291136&partnerID=8YFLogxK
M3 - Article
C2 - 15206729
AN - SCOPUS:1042291136
SN - 0065-2598
VL - 527
SP - 167
EP - 176
JO - Advances in Experimental Medicine and Biology
JF - Advances in Experimental Medicine and Biology
ER -