Calcium inhibits penetration of Alzheimer's Aβ1–42 monomers into the membrane

What is it about?

Aβ aggregation, calcium dysregulation, and membrane damage are Alzheimer's disease (AD) implications. To gain a detail of calcium ions' role in the full-length Aβ monomer's contact with the cellular membrane before their aggregation to elucidate the neurotoxicity mechanism. We found that Calcium ions do not allow Aβ1–42 penetration into the membranes nor contact of Aβ1–42-Cu2+ with the membranes. These pieces of information are corroborated by western blot experimental results of a higher concentration of calcium ions inhibiting the membrane pore formation by Aβ peptides.

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Photo by Josephina Kolpachnikof on Unsplash

Photo by Josephina Kolpachnikof on Unsplash

Why is it important?

We surprisingly noted: (1) Robust binding energies between the Aβ1–42 and membrane observed in simulations containing without calcium ions are two and a half fold lesser than in the simulation with calcium ions. Therefore, in the case of the absence of calcium ions, N-terminal residues of Aβ1–42 deeply penetrate from the surface to the center of the bilayer; in contrast to calcium ions presence, the N- and C-terminal residues are involved only in surface contacts through binding phosphate moieties. (2) Aβ1–42-Cu2+ actively participated in surface bilayer contacts without calcium ions. These contacts are prevented by forming a calcium bridge between Aβ1–42-Cu2+ and the DMPC bilayer in the case of calcium ions presence.

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