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Alzheimer’s Amyloid-β Oligomers Rescue Cellular Prion Protein Induced Tau Reduction via the Fyn Pathway
Alzheimer’s Amyloid-β Oligomers Rescue Cellular Prion Protein Induced Tau Reduction via the Fyn Pathway
- Source :
- ACS Chemical Neuroscience. 4:1287-1296
- Publication Year :
- 2013
- Publisher :
- American Chemical Society (ACS), 2013.
-
Abstract
- Amyloid-β (Aβ) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aβ oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aβ oligomers have been shown to specifically interact with cellular prion protein (PrP(C)) where the role of PrP(C) in AD is still not fully understood. To investigate the downstream mechanism of PrP(C) and Aβ oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP(C) and studied the effect under Aβ oligomer treatment. By Western blotting, we found that PrP(C) overexpression down-regulated tau protein and Aβ oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP(C), the high AD risk polymorphic allele in human prion gene. PrP(C) lacking the Aβ oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP(C) effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP(C)-induced tau reduction and Aβ oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aβ-PrP(C)-tau signaling. Overall, our results demonstrated that PrP(C) down-regulated tau via the Fyn pathway and the effect can be regulated by Aβ oligomers. Our study facilitated the understanding of molecular mechanisms among PrP(C), tau, and Aβ oligomers.
- Subjects :
- MAP Kinase Signaling System
Physiology
Recombinant Fusion Proteins
animal diseases
Cognitive Neuroscience
Tau protein
Mutation, Missense
Down-Regulation
tau Proteins
Proto-Oncogene Proteins c-fyn
Real-Time Polymerase Chain Reaction
Biochemistry
Mice
FYN
Alzheimer Disease
Cell Line, Tumor
Nitriles
mental disorders
Butadienes
medicine
Animals
Humans
Point Mutation
PrPC Proteins
RNA, Messenger
Binding site
Amyloid beta-Peptides
biology
Chemistry
MEK inhibitor
Wild type
Cell Biology
General Medicine
Transfection
medicine.disease
Molecular biology
Peptide Fragments
nervous system diseases
Pyrimidines
biology.protein
Signal transduction
Alzheimer's disease
Signal Transduction
Subjects
Details
- ISSN :
- 19487193
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- ACS Chemical Neuroscience
- Accession number :
- edsair.doi.dedup.....def471d43e8d65eca448854bb785c1f6
- Full Text :
- https://doi.org/10.1021/cn400085q