Pera M, Román S, Ratia M, Camps P, Muñoz-Torrero D, Colombo L, Manzoni C, Salmona M, Badia A, Clos M V
Departament de Farmacologia, de Terapèutica i de Toxicología, Institut Neurociències, Universitat Autónoma de Barcelona, Barcelona, Spain.
Biochem Biophys Res Commun. 2006 Jul 21;346(1):89-94. doi: 10.1016/j.bbrc.2006.04.187. Epub 2006 May 24.
Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-beta-protein (Abeta) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Abeta aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs.
乙酰胆碱酯酶（AChE）是老年斑的一种成分，在体外可促进β淀粉样蛋白（Aβ）原纤维的形成。阿尔茨海默病（AD）老年斑中存在朊蛋白（PrP），这促使我们评估AChE是否也能引发PrP肽的聚集。因此，我们研究了AChE对含有香豆素荧光探针（香豆素-PrP 106-126）的PrP肽（跨越106-126位残基）聚集的影响。香豆素-PrP 106-126聚集动力学显示聚集体最大尺寸（MSA）显著增加，这取决于AChE的浓度。通过偏振光和电子显微镜分析确定，AChE-PrP 106-126聚集体具有染色和光学淀粉样特性。碘化丙啶可显著抑制MSA，这表明AChE通过类似机制触发PrP 106-126和Aβ聚集。胡豆碱（AChE抑制剂）也显著降低了AChE诱导的MSA，揭示了一些AChE抑制剂作为一类新型潜在抗朊病毒药物的潜在价值。
