Fronza_2021_ACS.Chem.Neurosci_12_109

Reference

Title : Effect of QTC-4-MeOBnE Treatment on Memory, Neurodegeneration, and Neurogenesis in a Streptozotocin-Induced Mouse Model of Alzheimer's Disease - Fronza_2021_ACS.Chem.Neurosci_12_109
Author(s) : Fronza MG , Baldinotti R , Sacramento M , Gutierres J , Carvalho FB , Fernandes MDC , Sousa FSS , Seixas FK , Collares T , Alves D , Pratico D , Savegnago L
Ref : ACS Chem Neurosci , 12 :109 , 2021
Abstract :

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.

PubMedSearch : Fronza_2021_ACS.Chem.Neurosci_12_109
PubMedID: 33315382

Related information

Inhibitor QTC-4-MeOBnE

Citations formats

Fronza MG, Baldinotti R, Sacramento M, Gutierres J, Carvalho FB, Fernandes MDC, Sousa FSS, Seixas FK, Collares T, Alves D, Pratico D, Savegnago L (2021)
Effect of QTC-4-MeOBnE Treatment on Memory, Neurodegeneration, and Neurogenesis in a Streptozotocin-Induced Mouse Model of Alzheimer's Disease
ACS Chem Neurosci 12 :109

Fronza MG, Baldinotti R, Sacramento M, Gutierres J, Carvalho FB, Fernandes MDC, Sousa FSS, Seixas FK, Collares T, Alves D, Pratico D, Savegnago L (2021)
ACS Chem Neurosci 12 :109