A monoclonal antibody against acetylcholinesterase inhibits the formation of amyloid fibrils induced by the enzyme.
A monoclonal antibody (mAb) 25B1 directed against fetal bovine-serum acetylcholinesterase (FBS AChE) was used to examine the ability of the cholinergic enzyme to promote the assembly of amyloid-beta peptides (A beta) into Alzheimerś fibrils. This mAb binds to the peripheral anionic site of the enzyme and allosterically inhibits catalytic activity of FBS AChE. Several techniques, including thioflavine-T fluorescence, turbidity, and negative-staining at the electron microscopy level, were used to assess amyloid formation. Inhibition of amyloid formation was dependent on the molar ratio AChE:mAb 25B1, and at least 50% of the inhibition of the AChE promoting effect occurs at a molar ratio similar to that required for inhibition of the esterase activity. Our results suggest that mAb 25B1 inhibits the promotion of the amyloid fibril formation triggered by AChE by affecting the lag period of the A beta aggregation process.
Reyes
A E
AE
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Perez
D R
DR
Alvarez
A
A
Garrido
J
J
Gentry
M K
MK
Doctor
B P
BP
Inestrosa
N C
NC
D000110:Acetylcholinesterase / Q000276:immunology* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008854:Microscopy, Electron; D015394:Molecular Structure; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017354:Point Mutation
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C092395:amyloid beta-protein (12-28); D000110:Acetylcholinesterase