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

Bhattacharjee, Payel; Bhattacharyya, Debasish

doi:10.1074/jbc.m113.511410

Cited by 21 publications

(19 citation statements)

References 39 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was deduced from the fact that residues 162–167 of thrombin corresponded to 141–147 of RVV‐V (Fig. A); the latter showed homology to the sticky region ‘QKLVFFAE’ of Aβ42 . This information coupled to the previous initial observation that proteolytically digested thrombin could destabilize Aβ fibrillar aggregates (Fig.…”

Section: Resultsmentioning

confidence: 61%

“…It has previously been reported that small peptides derived from Russell’s viper venom (RVV)‐V potentially destabilized Aβ aggregate . Although RVV‐V and thrombin exhibit functional similarity, sequence wise they have limited homology.…”

Section: Resultsmentioning

confidence: 99%

“…Most of the β‐sheet breakers or hydrophobic peptide inhibitors of Aβ aggregate such as KLVFF (Table ) , KLVFF‐K 6 (hydrophobicity index, −13.7; molecular weight, 1420 Da) , FAEDVG‐K 6 (−22; 1410 Da) , LPFFD (4.3; 637.73 Da) , CTNIF (5.6; 596.71 Da) and Ac‐KQKLLLFLEE‐NH2 or LF peptide (−1.2; 1301 Da) exhibit hydrophobicity indices far below that of T3 (Table ). It also appears that the molecular weight of T3 is either comparable to or lesser than these peptides.…”

Section: Discussionmentioning

confidence: 99%

“…Aβ40/42 peptide (3.0 mg·mL −1 ) was dissolved in 100% HFIP (1,1,1,3,3,3 hexafluoro‐2‐propanol), sonicated in a water bath for 10 min, put into aliquots in polypropylene micro‐centrifuge tubes and kept at 25° C until it became a clear solution. The solution was then dried under vacuum and stored at −20° C. Prior to use, the thin film of HFIP‐treated Aβ40/42 peptides was dissolved in DMSO and diluted to 100 µ m in 10 m m Na‐phosphate, pH 7.5 containing 100 m m NaCl and incubated at 37° C with mild shaking for 7 days to form the fibrils . Aβ40/42‐soluble oligomers were prepared for slight modification as described after .…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Destabilization of β‐amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection

Bhattacharjee

Das

et al. 2020

The FEBS Journal

Self Cite

View full text Add to dashboard Cite

b-amyloid (Ab) aggregates involved in Alzheimer's disease (AD) are resistant to proteases but could be destabilized by small peptides designed to target specific hydrophobic regions of Ab that take part in aggregate assembly. Since thrombin and AD are intricately connected, and elastase modulates thrombin activity, elastase-digested thrombin peptides were verified for intervention in the Ab-aggregation pathway. Intact or elastase-digested thrombin destabilized Ab fibril, as demonstrated by thioflavin T assay. Peptides were synthesized employing thrombin as a template, of which, a hexapeptide (T3) showed maximum destabilization at 1 µM. ExPASy peptide cutter software coupled with mass spectrometric analysis confirmed the generation of T3 peptide from elastase-digested thrombin. TEM micrographs revealed that 30-day incubation of preformed Ab fibrils or monomers with T3 resulted in destabilization or inhibition, respectively, leading mostly to particles of 1.74 AE 0.17 nm, which roughly corresponded to Ab monomer. Surface plasmon resonance employing CM5 chip coupled with Ab40 mouse monoclonal antibody showed a drop in response when T3 was incubated with Ab fibrils between 2 and 8 h. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and confocal microscopy demonstrated the ability of T3 to rescue neuroblastoma cells from Ab oligomerinduced cytotoxic damage. Although no [Ab-T3] adduct could be detected by mass spectrometry, an initial interaction appeared to facilitate the process of destabilization/inhibition of aggregation. T3 was comparable to standard b-sheet breaker peptides, LPFFD and KLVFF in terms of Ab aggregate destabilization. High hydrophobicity values coupled with recognition and breaking elements make T3 a potential candidate for future therapeutic applications.

show abstract

Section: Resultsmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Destabilization of β‐amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection

Bhattacharjee

Das

et al. 2020

The FEBS Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another previous study revealed that FA5 polymorphisms confer an increased risk of ischemic stroke in younger adults (24). Furthermore, Bhattacharjee et al reported that the FA5 activator might be associated with Alzheimer's disease; the FA5 activator destabilized Aβ aggregates, which may be useful for disease prevention in the future (25). An earlier study found that the risk of dementia increased 2.11-fold in carriers of the FA5 Leiden mutation relative to subjects lacking this mutation [95% confidence interval [CI] 0.93-4.77].…”

Section: Discussionmentioning

confidence: 98%

Proteomic Analysis of Preoperative CSF Reveals Risk Biomarkers of Postoperative Delirium

et al. 2020

View full text Add to dashboard Cite

Objective: To analyze the proteome of preoperative cerebrospinal fluid (CSF) in older orthopedic patients with or without postoperative delirium (POD) using untargeted proteomics.Methods: A prospective cohort study was conducted. Eighty hip fracture patients aged ≥65 years were recruited. After successful spinal anesthesia, CSF was collected. The patients were divided into POD and No-POD groups based on the Confusion Assessment Method, and patients with POD were graded using the Memorial Delirium Assessment Scale (MDAS). Thirty No-POD patients were matched to 10 POD patients by age (±2 years) and Mini-Mental State Examination score (±2 scores). Label-free proteomic analysis was performed using a liquid chromatography coupled to mass spectrometry (LC-MS) workflow. Validation was performed using mass-spectrometry-based parallel reaction monitoring (PRM) for the 30 No-POD and 10 POD patients, as well as for an additional 5 POD patients. Bioinformatics were used to investigate possible relevant pathological mechanisms.Results: The incidence of POD in older orthopedic patients was 18.8% in our cohort of 80 patients. Proteomics results revealed 63 dysregulated CSF proteins, and PRM analysis validated these results. The preoperative CSF levels of both V-set and transmembrane domain-containing protein 2B (VSTM2B) and coagulation factor V (FA5) were positively correlated with MDAS scores on postoperative day 1 (r > 0.8, p < 0.05). Bioinformatic analysis revealed that several nervous-system-related pathways are relevant to POD development. Conclusion:We identified and validated several novel CSF proteins that are dysregulated in POD, and revealed several pathways that are relevant to POD development. Our results not only provide risk biomarkers for POD, but also give clues for further investigations into the pathological mechanisms of delirium. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900021533).

show abstract

Destabilization of Human Insulin Fibrils by Peptides of Fruit Bromelain Derived From Ananas comosus (Pineapple)

Das

Bhattacharyya²

2017

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers. These processes were followed fluorimetrically using Thioflavin T and 1-ANS, size-exclusion HPLC, dynamic light scattering, atomic force microscopy, and transmission electron microscopy. Sequences of insulin (A and B chains) and bromelain were aligned using Clustal W software to predict most probable sites of interactions. Synthetic tripeptides corresponding to the hydrophobic interactive sites of bromelain showed disaggregation of insulin suggesting specificity of interactions. The peptides GG and AAA serving as negative controls showed no potency in destabilization of aggregates. Disaggregation potency of the peptides was also observed when insulin was deposited on HepG2 liver cells where no formation of toxic oligomers occurred. Amyloidogenic des-octapeptide (B23-B30 of insulin) incapable of cell signaling showed cytotoxicity similar to insulin. This toxicity could be neutralized by bromelain derived peptides. FT-IR and far-UV circular dichroism analysis indicated that disaggregated insulin had structure distinctly different from that of its hexameric (native) or monomeric states. Based on the stoichiometry of interaction and irreversibility of disaggregation, the mechanism/s of the peptides and insulin interactions has been proposed. J. Cell. Biochem. 118: 4881-4896, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

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

Cited by 21 publications

References 39 publications

Destabilization of β‐amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection

Destabilization of β‐amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection

Proteomic Analysis of Preoperative CSF Reveals Risk Biomarkers of Postoperative Delirium

Destabilization of Human Insulin Fibrils by Peptides of Fruit Bromelain Derived From Ananas comosus (Pineapple)

Contact Info

Product

Resources

About