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Structural Insight into Melatonin's Influence on the Conformation of Aβ42 Dimer Studied by Molecular Dynamics
Wei Kang1,2, Yan Lu1,2, Judith C Etaka2
1School of Physics and Optoelectronic Engineering, Hainan University, Haikou 570228, China.
Abstract:
The accumulation of amyloid-beta (Aβ) oligomers is recognized as a potential culprit in Alzheimer's disease (AD). Experimental studies show that melatonin, a hormone that mainly regulates circadian rhythm and sleep, can interact with Aβ peptides and disrupt the formation of oligomers. However, how melatonin inhibits the oligomerization of soluble Aβ is unclear. Here, by computational simulations, we investigate the effect of different levels of melatonin on the conformation of the Aβ42 dimer. We find that the conformation of the Aβ42 dimer is dependent on melatonin levels. When melatonin is absent, the dimer mainly forms a parallel β-sheet in the CHC region. When one melatonin molecule is present, the overall conformation of the dimer does not change much, but the N-terminal of the dimer tends to adopt antiparallel β-sheets. When two melatoinin molecules are present, the Aβ42 dimer exhibits significant structural change, especially in its central region, resulting in a more compact conformation, and forms parallel β-sheets in the C-terminal. This conformational difference induced by different levels of melatoinin can shed light on the protective role of melatonin.
Insights
Melatonin impacts amyloid-beta (Aβ) 42 dimer structure, potentially inhibiting Alzheimer's disease (AD) progression. Computational studies reveal melatonin binding alters Aβ conformation, offering insights into its protective role.
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.
