Structural Insight into Melatonin's Influence on the Conformation of Aβ₄₂ Dimer Studied by Molecular Dynamics...

Area of Science:

• Biochemistry
• Neuroscience
• Computational Biology

Background:

• Amyloid-beta (Aβ) oligomer accumulation is implicated in Alzheimer's disease (AD) pathogenesis.
• Melatonin, a hormone regulating circadian rhythms, may inhibit Aβ oligomerization, but the mechanism is unclear.

Purpose of the Study:

• To investigate the effect of varying melatonin concentrations on the conformational structure of the Aβ42 dimer using computational simulations.
• To elucidate the molecular mechanisms by which melatonin may inhibit Aβ oligomerization.

Main Methods:

• Computational simulations were employed to model the Aβ42 dimer.
• The study analyzed conformational changes of the Aβ42 dimer at different melatonin concentrations (zero, one, and two molecules).

Main Results:

• Aβ42 dimer conformation is melatonin-dependent.
• In the absence of melatonin, the dimer forms a parallel β-sheet in the CHC region.
• One melatonin molecule minimally alters conformation, while two induce significant structural changes, including a more compact form and parallel β-sheets in the C-terminal.

Conclusions:

• Melatonin binding induces significant conformational changes in the Aβ42 dimer.
• These melatonin-induced structural alterations may explain its potential protective role against Aβ aggregation in Alzheimer's disease.