Crosslinking of amyloid-beta peptide to brain acetylcholinesterase.
Acetylcholinesterase (AChE) is the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine in the central nervous system. Recently, we have found that AChE promotes the assembly of amyloid-beta peptides (A beta) into Alzheimer fibrils. The action of AChE on the state of aggregation of the A beta peptide supposes a near neighbor relationship between these two molecules. In the present work, we have studied A beta-AChE interactions using the crosslinker reagent disuccinimidyl suberate (DSS), in the presence of [125I]-A beta peptide. The A beta-AChE complexes formed by crosslinkage were then analyzed by SDS-PAGE and autoradiography. We observed the formation of [125I] A beta-labeled complexes of 70, 160, 250, and 300 kDa corresponding to monomers, dimers, tetramers, and oligomers of AChE, respectively crosslinked with the A beta peptide. Our results suggest that AChE and the A beta peptide may be involved in physiologically relevant interactions, related to the pathogenesis of Alzheimer disease (AD).
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Departmento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
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D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D013388:Succinimides / Q000378:metabolism
D016229:Amyloid beta-Peptides; D003432:Cross-Linking Reagents; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D013388:Succinimides; D000110:Acetylcholinesterase; C019358:disuccinimidyl suberate