Abstract:
:Amyloid-beta (Aβ) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3β (GSK3β) pathway and deactivates GSK3β signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learning and memory performance, reduce Aβ and phosphorylated tau levels in mouse model of Alzheimer's disease (AD). However, it still remains unclear whether atorvastatin is responsible for regulation of AKT/GSK3β signaling and contributes to subsequent down-regulation of Aβ1-42 and phosphorylated tau in APP/PS1 transgenic (Tg APP/PS1) mice. Herein, we aimed to investigate the possible impacts of atorvastatin (10 mg/kg, p.o.) on the memory deficit by behavioral tests and changes of AKT/GSK3β signaling in hippocampus and prefrontal cortex by western blot test in Tg APP/PS1 mice. The results showed that treatment with atorvastatin significantly reversed the memory deficit in the Tg APP/PS1 mice in a novel object recognition and the Morris water maze tests. Moreover, atorvastatin significantly attenuated Aβ1-42 accumulation and phosphorylation of tau (Ser396) in the hippocampus and prefrontal cortex of Tg APP/PS1 mice. In addition, atorvastatin treatment also increased phosphorylation of AKT, inhibited GSK3β activity by increasing phosphorylation of GSK3β (Ser9) and decreasing the beta-site APP cleaving enzyme 1 (BACE1) expression. These results indicated that the memory ameliorating effect of atorvastatin may be, in part, by regulation the AKT/GSK3β signaling which may contribute to down-regulation of Aβ1-42 and tau hyperphosphorylation.
journal_name
Metab Brain Disjournal_title
Metabolic brain diseaseauthors
Zhou D,Liu H,Li C,Wang F,Shi Y,Liu L,Zhao X,Liu A,Zhang J,Wang C,Chen Zdoi
10.1007/s11011-016-9803-4subject
Has Abstractpub_date
2016-06-01 00:00:00pages
693-703issue
3eissn
0885-7490issn
1573-7365pii
10.1007/s11011-016-9803-4journal_volume
31pub_type
杂志文章abstract::Soluble amyloid-β protein (Aβ) oligomers have been recognized to be early and key intermediates in Alzheimer's disease-related synaptic dysfunction. In this study, using in vitro electrophysiology, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic oligosaccharide, w...
journal_title:Metabolic brain disease
pub_type: 杂志文章
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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abstract::Despite the existence of many preclinical studies, scientific evidence is lacking on the clinical use of alpha-lipoic acid (ALA) for central nervous system disorders. Therefore, we aimed at revising the literature concerning the use of ALA for the treatment of psychiatric and neurological conditions and to point out w...
journal_title:Metabolic brain disease
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