Pyridine-2,3-dicarboxylate, quinolinic acid, induces 1N4R Tau amyloid aggregation in vitro: Another evidence for the detrimental effect of the inescapable endogenous neurotoxin

Abstract

Quinolinic acid (QA) known as a neuro-active metabolite associated with the kynurenine pathway. At high concentrations, QA is often involved in the initiation and development of several human neurologic diseases, like Alzheimer's disease. Because of the QA action as the NMDA receptor, it is considered as a potent excitotoxin in vivo. Since it is probable that different mechanisms are employed by QA, activation of NMDA receptors cannot fully explain the revealed toxicity and it is even believed that there are multiple unknown mechanisms/targets leading to QA cytotoxicity. Herein we report accelerated amyloid oligomerization of 1N4R Tau under the effect of QA, in vitro, then the molecular structure, morphology and toxicity of the protein aggregate were documented by using various theoretical/experimental approaches. The possible mechanism of action of QA-induced Tau oligomerization has also been explored.

Keywords: Amyloid aggregation; Binding; Quinolinic acid; Tau; Toxicity mechanism.