Kynurenines, neurodegeneration and Alzheimer's disease

被引:61
作者
Kincses, Zsigmond Tamas
Toldi, Jozsef [2 ]
Vecsei, Laszlo [1 ]
机构
[1] Univ Szeged, Dept Neurol, Fac Med, Albert Szent Gyorgyi Clin Ctr, H-6725 Szeged, Hungary
[2] Univ Szeged, Dept Physiol Anat & Neurosci, H-6725 Szeged, Hungary
关键词
Alzheimer; kynurenine; oxidative stress; glutamate excitotoxicity; neuroinflammation; AMYLOID PRECURSOR PROTEIN; MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE; 3-HYDROXYANTHRANILIC ACID OXYGENASE; SYNAPTOSOMAL GLUTAMATE RELEASE; STIMULATION-INDUCED INCREASE; EXCITOTOXIN QUINOLINIC ACID; FREE-RADICAL GENERATION; RAT CORPUS STRIATUM; NITRO-L-ARGININE; BRAIN IN-VIVO;
D O I
10.1111/j.1582-4934.2010.01123.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Alzheimer's disease The kynurenine pathway Neuroactive kynurenines Enzymes of the kynurenine pathway Relations of kynurenines to the pathomechanism of AD Altered activation of the kynurenine pathway in AD Connection of oxidative stress and kynurenines Glutamatergic excitotoxicity Inflammation A future therapeutic approach: modulating the kynurenine pathway Concluding remarks Alzheimer's disease (AD) is one of the major causes of dementia. The pathogenesis of the disease is not entirely understood, but the amyloid beta peptide (A beta) and the formation of senile plaques seem to play pivotal roles. Oligomerization of the A beta is thought to trigger a cascade of events, including oxidative stress, glutamate excitotoxicity and inflammation. The kynurenine (KYN) pathway is the major route for the metabolism of the essential amino acid tryptophan. Some of the metabolites of this pathway, such as 3-hydroxykynurenine and quinolinic acid, are known to have neurotoxic properties, whereas others, such as kynurenic acid, are putative neuroprotectants. Among other routes, the KYN pathway has been shown to be involved in AD pathogenesis, and connections to other known mechanisms have also been demonstrated. Oxidative stress, glutamate excitotoxicity and the neuroinflammation involved in AD pathogenesis have been revealed to be connected to the KYN pathway. Intervention at these key steps may serve as the aim of potential therapy.
引用
收藏
页码:2045 / 2054
页数:10
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