World Library  

Add to Book Shelf
Flag as Inappropriate
Email this Book

Plos Biology : Sequestration of the Ab Peptide Prevents Toxicity and Promotes Degradation in Vivo, Volume 8

By Guo, Ming

Click here to view

Book Id: WPLBN0003940971
Format Type: PDF eBook :
File Size:
Reproduction Date: 2015

Title: Plos Biology : Sequestration of the Ab Peptide Prevents Toxicity and Promotes Degradation in Vivo, Volume 8  
Author: Guo, Ming
Volume: Volume 8
Language: English
Subject: Journals, Science, Biology
Collections: Periodicals: Journal and Magazine Collection, PLoS Biology
Publication Date:
Publisher: Plos


APA MLA Chicago

Guo, M. (n.d.). Plos Biology : Sequestration of the Ab Peptide Prevents Toxicity and Promotes Degradation in Vivo, Volume 8. Retrieved from

Description : Protein aggregation, arising from the failure of the cell to regulate the synthesis or degradation of aggregation-prone proteins, underlies many neurodegenerative disorders. However, the balance between the synthesis, clearance, and assembly of misfolded proteins into neurotoxic aggregates remains poorly understood. Here we study the effects of modulating this balance for the amyloid-beta (Ab) peptide by using a small engineered binding protein (ZAb3) that binds with nanomolar affinity to Ab, completely sequestering the aggregation-prone regions of the peptide and preventing its aggregation. Co-expression of ZAb3 in the brains of Drosophila melanogaster expressing either Ab42 or the aggressive familial Alzheimer9s disease (AD) associated E22G variant of Ab42 abolishes their neurotoxic effects. Biochemical analysis indicates that monomer Ab binding results in degradation of the peptide in vivo. Complementary biophysical studies emphasize the dynamic nature of Ab aggregation and reveal that ZAb3 not only inhibits the initial association of Ab monomers into oligomers or fibrils, but also dissociates pre-formed oligomeric aggregates and, although very slowly, amyloid fibrils. Toxic effects of peptide aggregation in vivo can therefore be eliminated by sequestration of hydrophobic regions in monomeric peptides, even when these are extremely aggregation prone. Our studies also underline how a combination of in vivo and in vitro experiments provide mechanistic insight with regard to the relationship between protein aggregation and clearance and show that engineered binding proteins may provide powerful tools with which to address the physiological and pathological consequences of protein aggregation.


Click To View

Additional Books

  • Plos Biology : Flux Analysis Uncovers Ke... (by )
  • Plos Biology : Desperately Seeking Stabl... (by )
  • Plos Biology : Dna Display II. Genetic M... (by )
  • Plos Biology : Francis Crick’s Legacy fo... (by )
  • Plos Biology : an Excitatory Loop with A... (by )
  • Plos Biology : a Close Look at Hearing R... (by )
  • Plos Biology : Species-specific Heteroch... (by )
  • Plos Biology : the Zebrafish Moonshine G... (by )
  • Plos Biology : Evolutionary Tinkering wi... (by )
  • Plos Biology : Experimental Evolution of... (by )
  • Plos Biology : Developmental Changes in ... (by )
  • Plos Biology : Improving Bioscience Rese... (by )
Scroll Left
Scroll Right


Copyright © World Library Foundation. All rights reserved. eBooks from World Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.