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Chem Biol Interact ; 315: 108884, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31678113

RESUMO

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.


Assuntos
Amiloide/metabolismo , Neurotoxinas/efeitos adversos , Agregados Proteicos/efeitos dos fármacos , Piridinas/efeitos adversos , Ácido Quinolínico/efeitos adversos , Doença de Alzheimer/metabolismo , Humanos , Cinurenina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
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