Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme.
Acetylcholinesterase (AChE), an important component of cholinergic synapses, colocalizes with amyloid-beta peptide (A beta) deposits of Alzheimer's brain. We report here that bovine brain AChE, as well as the human and mouse recombinant enzyme, accelerates amyloid formation from wild-type A beta and a mutant A beta peptide, which alone produces few amyloid-like fibrils. The action of AChE was independent of the subunit array of the enzyme, was not affected by edrophonium, an active site inhibitor, but it was affected by propidium, a peripheral anionic binding site ligand. Butyrylcholinesterase, an enzyme that lacks the peripheral site, did not affect amyloid formation. Furthermore, AChE is a potent amyloid-promoting factor when compared with other A beta-associated proteins. Thus, in addition to its role in cholinergic synapses, AChE may function by accelerating A beta formation and could play a role during amyloid deposition in Alzheimer's brain.
Inestrosa
N C
NC
Departamento de Biología Celular y Molecular Facultad de Ciencias Biológicas Pontificia Universidad Católica de Chile, Santiago, Chile.
Alvarez
A
A
Pérez
C A
CA
Moreno
R D
RD
Vicente
M
M
Linker
C
C
Casanueva
O I
OI
Soto
C
C
Garrido
J
J
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles; D001665:Binding Sites; D001921:Brain / Q000201:enzymology* / Q000648:ultrastructure; D002091:Butyrylcholinesterase / Q000378:metabolism; D002417:Cattle; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D009154:Mutation; D009454:Neurofibrils / Q000378:metabolism* / Q000648:ultrastructure; D011419:Propidium / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000378:metabolism
D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D013844:Thiazoles; C009462:thioflavin T; D011419:Propidium; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase