Interaction between synthetic amyloid-β-peptide (1-40) and its aggregation inhibitors studied by electrospray ionization mass spectrometry

• Published in: Journal of mass spectrometry Vol. 36; no. 11; pp. 1226 - 1229
• Main Authors: Skribanek, Zsolt, Baláspiri, Lajos, Mák, Marianna
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2001; Wiley
• Subjects: aggregation inhibitors; Amino Acid Sequence; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - chemistry; amyloid-β-peptide (1-40); Antioxidants - chemistry; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; electrospray ionization mass spectrometry; Medical sciences; melatonin; Melatonin - chemistry; Molecular Sequence Data; Neurology; Nicotine - chemistry; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - chemistry; protein-ligand interactions; Spectrometry, Mass, Electrospray Ionization; Melatonin; Senile plate; Peptides; Alzheimer disease; Molecular interaction; Neuroprotective agent; Electrospray; Aggregation; Prevention; Analysis method; Synthetic product; Cytoprotector; β Amyloid protein; Neurotransmitter; Degenerative disease; Inhibition; Mass spectrometry; Structural analysis
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/jms.243

It is generally postulated that amyloid‐β‐peptides play a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathological properties of these peptides, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of amyloid‐β‐peptides to form β‐sheet structures and/or amyloid fibrils. Amyloid‐β‐peptides are known to aggregate spontaneously in vitro with the formation of amyloid fibrils. The intervention on the amyloid‐β‐peptides aggregation process can be envisaged as an approach to stopping or slowing the progression of Alzheimer's disease. In the last few years a number of small molecules have been reported to interfere with the in vitro aggregation of amyloid‐β‐peptides. Melatonin, a hormone recently found to protect neurons against amyloid‐β‐peptide toxicity, interacts with amyloid‐β‐peptide (1–40) and amyloid‐β‐peptide (1–42) and inhibits the progressive formation of β‐sheet and/or amyloid fibrils. These interactions between melatonin and the amyloid peptides have been demonstrated by circular dichroism (CD) and electron microscopy for amyloid‐β‐peptide (1–40) and amyloid‐β‐peptide (1–42) and by nuclear magnetic resonance (NMR) spectroscopy for amyloid‐β‐peptide (1–40). Our electrospray ionization mass spectrometric (ESI‐MS) studies also proved that there is a hydrophobic interaction between amyloid‐β‐peptide (1–40) and melatonin and the proteolytic investigations suggested that the interaction took place on the 29–40 amyloid‐β‐peptide segment. The wide‐ranging application of these results would provide further information and help in biological research. Copyright © 2001 John Wiley & Sons, Ltd.