期刊
ACS CHEMICAL NEUROSCIENCE
卷 12, 期 1, 页码 109-122出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.0c00615
关键词
Alzheimer's disease; behavioral deficits; acetylcholinesterase; Na+/K+ ATPase; oxidative stress; neurogenesis; remyelination; multitarget
资金
- CNPq
- CAPES
- FAPERGS [PRONEM 16/2551-0000240-1, PqG:17/255100011046-9, FAPERGS/CAPES 04/2018 -DOCFIX18/2551-0000511-8]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES) [001]
QTC-4-MeOBnE shows potential anti-Alzheimer's disease effects through multiple pathways, including reversal of neuronal loss, reduction of oxidative stress, improvement of synaptic function, and promotion of adult neurogenesis and remyelination.
Growing evidence suggests that drugs targeting neurogenesis and myelinization could be novel therapeutic targets against Alzheimer's disease (AD). Intracerebroventricular (icv) injection of streptozotocin (STZ) induces neurodegeneration through multiple mechanisms ultimately resulting in reduced adult neurogenesis. Previously, the multitarget compound QTC-4-MeOBnE (1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide) demonstrated beneficial effects in preclinical models of AD. Here we investigated its pharmacokinetics profile and the effect on memory impairments and neurodegeneration induced by STZ. Two icv injections of STZ resulted in significant cognitive and memory impairments, assessed by novel object recognition, Y-maze, social recognition, and step-down passive avoidance paradigms. These deficits were reversed in STZ-injected mice treated with QTC-4-MeOBnE. This effect was associated with reversion of neuronal loss in hippocampal dentate gyrus, reduced oxidative stress, and amelioration of synaptic function trough Na+/K+ ATPase and acetylcholinesterase activities. Furthermore, brains from QTC-4-MeOBnE-treated mice had a significant increase in adult neurogenesis and remyelination through Prox1/NeuroD1 and Wnt/beta-catenin pathways. Overall, our findings support the potential anti-AD effect of QTC-4-MeOBnE through multiple pathways, all of which have been involved in the onset and progression of the disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据