Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

9.2K
Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
9.2K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Droplet Fusion as a Relaxation Process: Comparison with Shape Recovery of Newtonian and Viscoelastic Droplets.

ArXiv·2026
Same author

Complex Effects of Salt on Small-Angle X-ray Scattering of BSA Originate from the Interplay of Ions and Hydration Water.

The journal of physical chemistry letters·2026
Same author

Counteraction of HMGB1 at ss-dsDNA junctions maintains liquidity of protamine-DNA co-condensates.

bioRxiv : the preprint server for biology·2026
Same author

Complex Effects of Salt on Small-Angle X-ray Scattering of BSA Originate From the Interplay of Ions and Hydration Water.

ArXiv·2026
Same author

A membrane insertion code for intrinsically disordered proteins.

bioRxiv : the preprint server for biology·2026
Same author

Conformations and sequence determinants in the lipid binding of an adhesive peptide derived from Vibrio cholerae biofilms.

PLoS pathogens·2026

Related Experiment Video

Updated: May 22, 2025

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

11.8K

Membrane-assisted Aβ40 aggregation pathways.

Fidha Nazreen Kunnath Muhammedkutty1, Huan-Xiang Zhou1,2,3

  • 1Department of Chemistry, University of Illinois Chicago, Chicago, IL, USA.

Cell Reports. Physical Science
|March 14, 2025
PubMed
Summary

Alzheimer's disease (AD) involves amyloid-beta (Aβ) aggregation on cell membranes. Molecular dynamics simulations reveal how GM1 ganglioside, cholesterol, and specific Aβ residues influence fibril formation, offering insights for AD therapies.

More Related Videos

Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain
09:35

Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain

Published on: October 24, 2017

12.0K
Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
08:53

Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids

Published on: March 21, 2025

263

Related Experiment Videos

Last Updated: May 22, 2025

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

11.8K
Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain
09:35

Enrichment of Detergent-insoluble Protein Aggregates from Human Postmortem Brain

Published on: October 24, 2017

12.0K
Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
08:53

Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids

Published on: March 21, 2025

263

Area of Science:

  • Neuroscience
  • Biochemistry
  • Computational Biology

Background:

  • Alzheimer's disease (AD) pathogenesis involves amyloid-beta (Aβ) peptide aggregation into toxic oligomers and fibrils.
  • Cell membranes significantly accelerate Aβ nucleation, yet mechanisms of membrane-assisted aggregation remain poorly understood.

Purpose of the Study:

  • To structurally and energetically characterize Aβ40 aggregation intermediates on cell membranes using molecular dynamics (MD) simulations.
  • To elucidate the roles of specific membrane components and Aβ residues in initiating and stabilizing fibril formation.

Main Methods:

  • Extensive molecular dynamics (MD) simulations of amyloid-beta 40 (Aβ40) peptides interacting with model cell membranes.
  • Analysis of intermediate structures and energetic contributions during membrane-assisted Aβ aggregation.

Main Results:

  • GM1 ganglioside and cholesterol stabilize membrane-embedded β sheets, crucial for early aggregation.
  • Specific residues (Y10, K28) mediate the release of an oligomeric seed, which subsequently forms distinct fibril structures (open or R-shaped).
  • Fibril stabilization involves interfaces between straight (Q15-D23) and bent (A30-V36) β sheets.

Conclusions:

  • This study provides a comprehensive view of Aβ40 membrane-assisted aggregation pathways.
  • Findings highlight the critical roles of membrane lipids and Aβ sequence in fibril formation, offering potential therapeutic targets for Alzheimer's disease.
  • The work aids in understanding disease-specific polymorphisms in amyloidogenic proteins.