title: Factor V activator from Daboia russelli russelli venom destabilizes β-amyloid aggregate, the hallmark of Alzheimer disease.
abstract: Formation of plaque by fibrils of β-amyloid (Aβ) peptide in the brain is the characteristic feature of Alzheimer disease (AD). Inhibition of the process of aggregate formation from Aβ-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 Aβ 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 thioflavin T assay. The alternate hypothesis that small peptides derived from RVV-V destabilize 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 of Aβ 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 venom-derived peptides offer an encouraging opportunity to prevent amyloidosis and may provide information to combat AD.
authors.affiliation: From the Division of Structural Biology and Bioinformatics, Council of Scientific and Industrial Research, Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, India. Electronic address: payel.iicb@gmail.com.
authors.forename: Payel
authors.initials: P
authors.lastname: Bhattacharjee
authors.affiliation: From the Division of Structural Biology and Bioinformatics, Council of Scientific and Industrial Research, Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, India. Electronic address: debasish@iicb.res.in.
authors.forename: Debasish
authors.initials: D
authors.lastname: Bhattacharyya
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D010447:Peptide Hydrolases / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D014757:Viper Venoms / Q000737:chemistry*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010455:Peptides; D014757:Viper Venoms; D010447:Peptide Hydrolases; C121422:factor V activating enzyme
keywords: Aggregation; Amyloid; Neurodegenerative Diseases; Peptides; Russell's Viper Venom Factor V Activator; Toxins