Back to Search
Start Over
The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV) cleaves amyloid-β
- Source :
- PLoS ONE, Vol 5, Iss 12, p e15645 (2010), PLoS ONE
- Publication Year :
- 2010
- Publisher :
- Public Library of Science (PLoS), 2010.
-
Abstract
- Background The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV) is responsible for the processing of the viral polyprotein into functional proteins. NIa was previously shown to possess a relatively strict substrate specificity with a preference for Val-Xaa-His-Gln↓, with the scissile bond located after Gln. The presence of the same consensus sequence, Val12-His-His-Gln15, near the presumptive α-secretase cleavage site of the amyloid-β (Aβ) peptide led us to hypothesize that NIa could possess activity against Aβ. Methodology/Principal Findings Western blotting results showed that oligomeric as well as monomeric forms of Aβ can be degraded by NIa in vitro. The specific cleavage of Aβ was further confirmed by mass spectrometry analysis. NIa was shown to exist predominantly in the cytoplasm as observed by immunofluorescence microscopy. The overexpression of NIa in B103 neuroblastoma cells resulted in a significant reduction in cell death caused by both intracellularly generated and exogenously added Aβ. Moreover, lentiviral-mediated expression of NIa in APPsw/PS1 transgenic mice significantly reduced the levels of Aβ and plaques in the brain. Conclusions/Significance These results indicate that the degradation of Aβ in the cytoplasm could be a novel strategy to control the levels of Aβ, plaque formation, and the associated cell death.
- Subjects :
- Cytoplasm
Proteases
Cell Survival
medicine.medical_treatment
Molecular Sequence Data
Biomedical Engineering
lcsh:Medicine
Bioengineering
Mice, Transgenic
Cleavage (embryo)
Gene Expression Regulation, Enzymologic
Substrate Specificity
Mice
Viral Proteins
Scissile bond
Mosaic Viruses
Cell Line, Tumor
Drug Discovery
Endopeptidases
medicine
Animals
Turnip mosaic virus
Amino Acid Sequence
lcsh:Science
Biology
Peptide sequence
Clinical Genetics
Neurons
Amyloid beta-Peptides
Multidisciplinary
Protease
Mosaic virus
biology
Brassica napus
lcsh:R
Gene Therapy
biology.organism_classification
Molecular biology
Rats
Disease Progression
Medicine
lcsh:Q
Research Article
Biotechnology
Subcellular Fractions
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....f292dd1ec6880f6ac8ca048e8e39c84d