Amyloid-cholinesterase interactions. Implications for Alzheimer's disease.
Acetylcholinesterase is an enzyme associated with senile plaques. Biochemical studies have indicated that acetylcholinesterase induces amyloid fibril formation by interaction throughout the peripherical anionic site of the enzyme forming highly toxic acetylcholinesterase-amyloid-beta peptide (Abeta) complexes. The pro-aggregating acetylcholinesterase effect is associated with the intrinsic amyloidogenic properties of the corresponding Abeta peptide. The neurotoxicity induced by acetylcholinesterase-Abeta complexes is higher than the that induced by the Abeta peptide alone, both in vitro and in vivo. The fact that acetylcholinesterase accelerates amyloid formation and the effect is sensitive to peripherical anionic site blockers of the enzyme, suggests that specific and new acetylcholinesterase inhibitors may well provide an attractive possibility for treating Alzheimer's disease. Recent studies also indicate that acetylcholinesterase induces the aggregation of prion protein with a similar dependence on the peripherical anionic site.
Inestrosa
Nibaldo C
NC
CRCP Biomedical Center, Pontificia Universidad Católica de Chile, Santiago, Chile. ninestrosa@bio.puc.cl
Dinamarca
Margarita C
MC
Alvarez
Alejandra
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002802:Cholinesterases / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D011485:Protein Binding
D000682:Amyloid; D000110:Acetylcholinesterase; D002802:Cholinesterases