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Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
Published on: May 13, 2010
β- N-Methylamino-l-alanine (BMAA) Not Involved in Alzheimer's Disease
1Department of Chemistry , University of Calgary , 2500 University Dr. NW , Calgary , Alberta , Canada T2N 1N4.
The Journal of Physical Chemistry. B
|April 14, 2018
Summary
Beta-N-Methylamino-L-alanine (BMAA), a neurotoxin from blue-green algae, may link to neurodegenerative diseases. This study found BMAA can bind noncovalently to proteins, but not by replacing serine in beta-amyloid peptides.
Area of Science:
- Neuroscience
- Biochemistry
- Computational Chemistry
Background:
- Beta-N-Methylamino-L-alanine (BMAA) is a neurotoxin produced by blue-green algae, potentially entering the human diet through seafood.
- BMAA is found in both monomeric and protein-bound forms in biological samples.
- The protein-bound form of BMAA has been hypothesized to arise from genetic misincorporation in place of serine, leading to protein misfolding and neurodegeneration.
Purpose of the Study:
- To investigate the potential for noncovalent binding of BMAA to proteins using quantum mechanical calculations.
- To explore the interaction of BMAA with beta-amyloid peptide, a key player in Alzheimer's disease, using molecular dynamics simulations.
- To determine if BMAA incorporation in place of serine residues in beta-amyloid peptide affects its aggregation into neurotoxic oligomers.
Main Methods:
- Quantum mechanical calculations on model systems to assess BMAA's binding affinity to proteins.
- Molecular dynamics simulations to model the interaction between BMAA and beta-amyloid peptide.
- Analysis of conformational dynamics of beta-amyloid peptide with and without BMAA incorporation.
Main Results:
- Quantum mechanical calculations demonstrated that BMAA can bind to proteins with high affinity through noncovalent interactions.
- Molecular dynamics simulations did not identify any stable noncovalently bound complexes between BMAA and beta-amyloid peptide.
- Replacing serine residues in beta-amyloid peptide with BMAA did not alter the peptide's conformational dynamics or aggregation behavior.
Conclusions:
- BMAA can bind noncovalently to proteins, offering a potential mechanism for its presence in biological systems.
- The theory of BMAA misincorporation in place of serine in beta-amyloid peptide is not supported by these simulations.
- These findings suggest that BMAA's role in Alzheimer's disease may not involve direct substitution for serine in beta-amyloid peptides.
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