Kynurenines, neurodegeneration and Alzheimer's disease.
Bottom Line: 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.Intervention at these key steps may serve as the aim of potential therapy.
Affiliation: Department of Neurology, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.Show MeSH
Related in: MedlinePlus
Mentions: The first breakthrough towards an understanding of the pathomechanism of AD was the identification of amyloid β-peptide (Aβ) in the meningeal vessels of AD patients and later in the senile plaques [12–14]. Aβ is the product of the degradation of the amyloid precursor protein (APP), the gene of which is located on chromosome 21 [15–18]. The APP is cleaved by β- and γ-secretases. Mutations of the presenilin 1 and 2 (the subcomponents of γ-secretase),  and the APP [20–24] result in the accumulation of the amyloidogenic form of Aβ and the clinical picture of AD, but the genetically determined form of the disease is relatively rare. However, the oligomerization of Aβ seems to be the pivotal step in the pathogenesis of AD but the role of it was also questioned recently . An intimate interaction between the oligomerization of Aβ and several other pathomechanistic mechanisms leads to the hyperphosphorylation of τ-proteins, the formation of neurofibrillary tangles, synaptic degeneration, oxidative stress, microglial and astrocytic activation, activation of the apoptotic cascade, cell death and transmitter deficiency (Figs 1 and 2). The aim of therapeutic approaches is to modify one or other of these individual steps, generally by anti-amyloid, neuroprotective or neurorestorative means.
Affiliation: Department of Neurology, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.