tailieunhanh - Báo cáo khoa học: Amyloid–cholinesterase interactions Implications for Alzheimer’s disease

Acetylcholinesterase is an enzyme associated with senile plaques. Biochemi-cal studies have indicated that acetylcholinesterase induces amyloid fibril formation by interaction throughout the peripherical anionic site of the enzyme forming highly toxic acetylcholinesterase–amyloid-bpeptide (Ab) complexes. | ỊFEBS Journal MINIREVIEW Amyloid-cholinesterase interactions Implications for Alzheimer s disease Nibaldo C. Inestrosa Margarita C. Dinamarca and Alejandra Alvarez CRCP BiomedicalCenter Pontificia Universidad Catolica de Chile Santiago Chile Keywords acetylcholinesterase acetylcholinesterase-Ap complexes Alzheimer s disease amyloid formation amyloid oligomers Ap-amyloid fibrils butyrylcholinesterase molecular chaperone neurotoxicity peripherical anionic site Correspondence N. C. Inestrosa CRCP BiomedicalCenter Pontificia Universidad Catolica de Chile Alameda 340 Santiago Chile Fax 56 2 686 2959 Tel 56 2 686 2724 E-mail ninestrosa@ Received 12 October 2007 accepted 12 December 2007 doi 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-p peptide Ap complexes. The pro-aggregating acetylcholinesterase effect is associated with the intrinsic amyloidogenic properties of the corresponding Ap peptide. The neurotoxicity induced by acetylcholinesterase-Ap complexes is higher than the that induced by the Ap 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. Alzheimer s disease is a progressive and irreversible neurodegenerative disorder that has emerged as the most prevalent form of late-life mental failure in humans. Although a small percentage of Alzheimer s disease cases involve .

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