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Factor V Activator from Daboia russelli russelli Venom Destabilizes �-Amyloid Aggregate, the Hallmark of Alzheimer Disease*

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Title Factor V Activator from Daboia russelli russelli Venom
Destabilizes �-Amyloid Aggregate, the Hallmark of
Alzheimer Disease*
 
Creator Bhattacharjee, Payel
Bhattacharyya, Debasish
 
Subject Structural Biology & Bioinformatics
 
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
 
Publisher American Society for Biochemistry and Molecular Biology
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
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,.
 
Relation http://www.eprints.iicb.res.in/2421/