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Inhibition of glycogen synthase kinase-3β by Angelica sinensis extract decreases β-amyloid-induced neurotoxicity and tau phosphorylation in cultured cortical neurons
- Source :
- Journal of neuroscience research. 89(3)
- Publication Year :
- 2010
-
Abstract
- Increasing evidence has shown that β-amyloid (Aβ) induces hyperphosphorylation of tau and contributes to Aβ toxicity. Recently, tau hyperphosphorylation by glycogen synthase kinase-3β (GSK-3β) activation has been emphasized as one of the pathogenic mechanisms of Alzheimer's disease (AD). The phosphoinositide 3 kinase (PI3K)/Akt pathway is known as an upstream element of GSK-3β. The inhibitory control of GSK-3β, via the PI3K/Akt pathway, is an important mechanism of cell survival. In the present study, we investigated the neuroprotective effects of Angelica sinensis (AS), a traditional Chinese herbal medicine, against Aβ(1-42) toxicity in cultured cortical neurons and also the potential involvement of PI3K/Akt/GSK-3β signal pathway. We revealed that AS extract significantly attenuated Aβ(1-42) -induced neurotoxicity and tau hyperphosphorylation at multiple AD-related sites in a dose-dependent manner. Simultaneously, it increased the levels of phospho-Ser(473) -Akt and down-regulated GSK-3β activity by PI3K activation. The neuroprotective effects of AS extract against Aβ(1-42) -induced neurotoxicity and tau hyperphosphorylation were blocked by LY294002 (10 μM), a PI3K inhibitor. In addition, AS extract reversed the Aβ(1-42) -induced decrease in phosphorylation cyclic AMP response element binding protein (CREB), which could be blocked by the PI3K inhibitor. These results suggest that AS-mediated neuroprotection against Aβ toxicity is likely mediated by the PI3K/Akt/GSK-3β signal pathway.
- Subjects :
- medicine.medical_specialty
Hyperphosphorylation
Apoptosis
tau Proteins
Pharmacology
Cellular and Molecular Neuroscience
Glycogen Synthase Kinase 3
GSK-3
Internal medicine
medicine
Animals
Enzyme Inhibitors
Phosphorylation
Rats, Wistar
Glycogen synthase
Protein kinase B
GSK3B
PI3K/AKT/mTOR pathway
Cells, Cultured
Cerebral Cortex
Neurons
Analysis of Variance
Phosphoinositide 3-kinase
Amyloid beta-Peptides
Glycogen Synthase Kinase 3 beta
biology
Dose-Response Relationship, Drug
Neurotoxicity
Angelica sinensis
medicine.disease
Peptide Fragments
Rats
Enzyme Activation
Endocrinology
Animals, Newborn
biology.protein
Benzimidazoles
Plant Preparations
Lithium Chloride
Signal Transduction
Subjects
Details
- ISSN :
- 10974547
- Volume :
- 89
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of neuroscience research
- Accession number :
- edsair.doi.dedup.....d44f05d362d7f2688f068909a32007aa