Interaction between synthetic amyloid-beta-peptide (1-40) and its aggregation inhibitors studied by electrospray ionization mass spectrometry.
It is generally postulated that amyloid-beta-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-beta-peptides to form beta-sheet structures and/or amyloid fibrils. Amyloid-beta-peptides are known to aggregate spontaneously in vitro with the formation of amyloid fibrils. The intervention on the amyloid-beta-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-beta-peptides. Melatonin, a hormone recently found to protect neurons against amyloid-beta-peptide toxicity, interacts with amyloid-beta-peptide (1-40) and amyloid-beta-peptide (1-42) and inhibits the progressive formation of beta-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-beta-peptide (1-40) and amyloid-beta-peptide (1-42) and by nuclear magnetic resonance (NMR) spectroscopy for amyloid-beta-peptide (1-40). Our electrospray ionization mass spectrometric (ESI-MS) studies also proved that there is a hydrophobic interaction between amyloid-beta-peptide (1-40) and melatonin and the proteolytic investigations suggested that the interaction took place on the 29-40 amyloid-beta-peptide segment. The wide-ranging application of these results would provide further information and help in biological research.
Skribanek
Z
Z
Gedeon Richter Ltd, P.O. Box 27, H-1475 Budapest 10, Hungary. zsolt.skribanek@unitis.hu
Baláspiri
L
L
Mák
M
M
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry; D008550:Melatonin / Q000737:chemistry; D008969:Molecular Sequence Data; D009538:Nicotine / Q000737:chemistry; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D009538:Nicotine; D008550:Melatonin