{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:44:32Z","timestamp":1790131472481,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,8,24]],"date-time":"2013-08-24T00:00:00Z","timestamp":1377302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>As a molecular chaperone, acetylcholinesterase (<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>Ch<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>; EC 3.1.1.7) plays a critical role in the pathogenesis of Alzheimer's disease (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>). The peripheral anionic site (<jats:styled-content style=\"fixed-case\">PAS<\/jats:styled-content>) of<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>has been indicated as the amyloid\u2010\u03b2 (A\u03b2) binding domain. The goal of this study was to determine other motifs in<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>involved in<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 aggregation and deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The \u03b2\u2010hairpin in monomeric<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 is the key motif of nucleation\u2010dependent<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 self\u2010aggregation. As<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>could induce<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 aggregation and deposition, we searched<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>for \u03b2\u2010hairpin structures. In<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>11\u2010specific dot blot assay,<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>was detected by an oligomer\u2010specific antibody<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>11, implying the existence of \u03b2\u2010hairpin structures in<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>as \u03b2\u2010hairpin was the core motif of oligomers. A molecular superimposing approach further revealed that the N\u2010terminal region, from Glu7 to Ile20, in<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>7\u201320) was similar to the \u03b2\u2010hairpin domain in<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2. The results of further dot blot assays, thioflavin T fluorescence assays, and electron microscopy imaging experiments, indicated that the N\u2010terminal synthetic peptide<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><jats:sub>7\u201320<\/jats:sub>had nearly the same ability as<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>with regard to triggering<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 aggregation and deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>7\u201320, a \u03b2\u2010hairpin region in<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>, might be a new motif in<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>capable of triggering<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u03b2 aggregation and deposition. This finding will be helpful to design new and more effective A\u03b2 aggregation inhibitors for<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12161","type":"journal-article","created":{"date-parts":[[2013,8,24]],"date-time":"2013-08-24T15:40:41Z","timestamp":1377358841000},"page":"59-66","source":"Crossref","is-referenced-by-count":16,"title":["A New Motif in the N\u2010Terminal of Acetylcholinesterase Triggers Amyloid\u2010\u03b2 Aggregation and Deposition"],"prefix":"10.1111","volume":"20","author":[{"given":"Li\u2010Na","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Medical Sciences Shanghai JiaoTong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Medical Sciences Shanghai JiaoTong 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