Small static electric field strength promotes aggregation-prone structures in amyloid-β(29-42)

Area of Science:

• Neuroscience
• Biophysics
• Computational Biology

Background:

• Alzheimer's disease is characterized by amyloid beta (Aβ) plaque formation in the central nervous system.
• Aβ aggregation is complex, influenced by factors like pH, temperature, and concentration.
• The effect of static electric fields (EFs) on amyloid aggregation is understudied, despite potential therapeutic applications.

Purpose of the Study:

• To investigate the influence of a biologically relevant static electric field (20 mV/nm) on the conformation of Aβ₂₉₋₄₂ dimers.
• To understand the role of EFs in the early stages of amyloid aggregation.

Main Methods:

• Atomistic simulations of Aβ₂₉₋₄₂ dimers in aqueous solution.
• Utilizing 7 μs non-equilibrium molecular dynamics simulations.
• Analyzing the conformational changes induced by a static electric field.

Main Results:

• A static electric field of 20 mV/nm significantly promotes the formation of β-hairpins in Aβ₂₉₋₄₂ dimers.
• β-hairpins are considered crucial intermediate structures in Aβ aggregation.
• The applied EF influences the conformational landscape of the Aβ dimer.

Conclusions:

• Static electric fields can play a substantial role in modulating amyloid-beta aggregation pathways.
• Structural biology experiments under controlled EF conditions may reduce conformational heterogeneity of Aβ dimers.
• This research provides insights into disease-causing structures and potential EF-based therapeutic interventions for neurodegenerative diseases.