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A Monoclonal Antibody against Acetylcholinesterase Inhibits the Formation of Amyloid Fibrils Induced by the Enzyme

https://doi.org/10.1006/bbrc.1997.6357Get rights and content

Abstract

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-β peptides (Aβ) 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 Aβ aggregation process.

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    All these inhibitors interact with PAS of AChE whereas catalytic site-only binding inhibitors such as tacrine and edrophonium were not able to inhibit AChE-induced Aβ aggregation [59]. Also, monoclonal antibody directed towards the PAS of AChE has inhibited the amyloid fibril formation triggered by AChE [58]. Hence, the interaction of AST-SAC with various amino acids present along the active site gorge, in particular with catalytic site and PAS is imperative, since AST-SAC might also inhibit the AChE-induced Aβ aggregation.

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R. D. TerryR. KatzmanK. L. Bick, Eds.

1

To whom correspondence should be addressed at Molecular Neurobiology Unit, Catholic University of Chile, P.O. Box 114-D, Santiago, Chile. Fax: 56-2-6862717.

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