ReferenceID 1598

The neuroprotective effects of phosphocreatine on Amyloid Beta 25-35-induced differentiated neuronal cell death through inhibition of AKT /GSK-3β /Tau/APP /CDK5 pathways in vivo and vitro

Free Radic Biol Med

Alzheimer (AD) is a degenerative disease that can lead memory loss and behavioral dysfunction. Abeta protein and phosphorylation of Tau protein are related to the onset of AD. However, at present, its treatment and drugs

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Reference Id
1598
Evidence Id
18188
Core Evidence Id
18188
Source Reference Id
3202
Herb2 Reference Id
HBREF003999
Subject Paper Key
HBIN021664_33131696
Pubmed Id
33131696
Doi
10.1016/j.freeradbiomed.2020.10.003
Paper Title
The neuroprotective effects of phosphocreatine on Amyloid Beta 25-35-induced differentiated neuronal cell death through inhibition of AKT /GSK-3β /Tau/APP /CDK5 pathways in vivo and vitro
Paper Abstract
Alzheimer (AD) is a degenerative disease that can lead memory loss and behavioral dysfunction. Abeta protein and phosphorylation of Tau protein are related to the onset of AD. However, at present, its treatment and drugs are limited. The purpose of our study is to evaluate whether phosphocreatine (PCr) could protect neuronal injury induced by Abeta protein in vivo and in vitro through AKT/GSK-3beta/Tau/APP/CDK5 pathways. Differentiated PC-12 cells were cultured with Abeta25-35 for 24 h, while the mice were injected with D-Galactose for eight weeks, both of them were pretreated with PCr for 2 h. The results showed PCr could obviously induce cells and hippocampus apoptosis using DAPI and TUNEL. PCr decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of superoxide dismutase (SOD). Besides, the apoptosis pathway was detected using Western blot, showing that PCr could significantly reduce caspase-3, caspase-9, Bcl-2/Bax expression in vivo and in vitro. At the same time, PCr could decreased Ca2+ and apoptosis by Flow Cytometry in PC-12 cells. We observed that the morphological alteration of hippocampus injury was mitigated with the pretreatment of PCr. Furthermore, PCr pretreatment could decrease Abeta25-35-induced PC-12 cells apoptosis with APP cDNA transfection, which up-regulated AKT/GSK-3beta/CDK5 pathways and induced Tau phosphorylation. In summary, PCr could reduce Abeta25-35 toxicity to protect neuronal cells via AKT/GSK-3beta/CDK5 pathways.
Journal
Free Radic Biol Med
Publish Year
2021
Experiment Subject
mouse; pc-12 cells
Experiment Type
Cell Experiment
Phenotype Related
Alzheimer; Memory Loss; Degenerative Disease; Behavioral Dysfunction
Paper Title Cn
Paper Title En
The neuroprotective effects of phosphocreatine on Amyloid Beta 25-35-induced differentiated neuronal cell death through inhibition of AKT /GSK-3β /Tau/APP /CDK5 pathways in vivo and vitro
Bilingual Status
semi_complete