Factor V Activator from Daboia russelli russelli Venom Destabilizes �-Amyloid Aggregate, the Hallmark of Alzheimer Disease*
EPrints@IICB
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Title |
Factor V Activator from Daboia russelli russelli Venom Destabilizes �-Amyloid Aggregate, the Hallmark of Alzheimer Disease* |
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Creator |
Bhattacharjee, Payel
Bhattacharyya, Debasish |
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Subject |
Structural Biology & Bioinformatics
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Description |
Formation of plaque by fibrils of �-amyloid (A�) peptide in the brain is the characteristic feature of Alzheimer disease (AD). Inhibition of the process of aggregate formation from A�-monomer and destabilization of the aggregate could be useful for prevention and propagation of the disease respectively. Russell’s viper venom (RVV) contains protein(s) that destabilize A� aggregates as revealed from the thioflavin T assay. The active component was identified as factor V activator (RVV-V). Among the possible mechanisms of destabilization, RVV-V-mediated proteolysis was ruled out from mass spectrometric data and the thioflavinTassay. The alternate hypothesis that small peptides derived fromRVV-Vdestabilize the aggregate is better supported by experimental results. Six small peptides were synthesized using RVV-V as the template, and three unrelated peptides were synthesized to serve as controls. Destabilization ofA� aggregate by these peptides was studied using spectrofluorometric assays, atomic force microscopy, transmission electron microscopy, and confocal microscopy. Among the peptides, CTNIF and the mixture of the six peptides were most potent in converting the aggregates to the monomeric state and thus, preventing cytotoxicity in SH-SY5Y human neuroblastoma cells. The control peptides failed to show similar effects. Moreover, some of these peptides are stable in blood for 24 h. Therefore, these venomderived peptides offer an encouraging opportunity to prevent amyloidosis and may provide information to combat AD |
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Publisher |
American Society for Biochemistry and Molecular Biology
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Date |
2013
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/2421/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY__Volume__288____Issue__42____Pages__30559%2D30570.pdf
Bhattacharjee, Payel and Bhattacharyya, Debasish (2013) Factor V Activator from Daboia russelli russelli Venom Destabilizes �-Amyloid Aggregate, the Hallmark of Alzheimer Disease*. The Journal of Biological Chemistry, 288 ( 42). 30559-30570,. |
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Relation |
http://www.eprints.iicb.res.in/2421/
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