Sabaté Raimon, Estelrich Joan
Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Avda. Joan XXIII s/n, 08028 Barcelona, Catalonia, Spain.
J Phys Chem B. 2005 Jun 2;109(21):11027-32. doi: 10.1021/jp050716m.
Alzheimer's disease (AD) is characterized by the deposition of fibrillar deposits formed by the amyloid beta (Abeta) peptide. The most widely accepted model of fibrillogenesis of Abeta affirms that fibrillogenesis occurs in two distinct stages, nucleation and elongation. A modification of the model includes the formation of micelles. We have demonstrated with accurate experimental determinations the existence of aggregates with micellar properties (namely, the critical micellar concentration, CMC, and aggregation number). Values of the CMC were obtained by analysis of surface tension (17.5 microM) and changes in the fluorescence of pyrene (17.6 microM), respectively. The average aggregation number determined by fluorescence quenching was 25, and it was independent of peptide concentration. The presence of micelles implies that above the CMC all excess peptide is incorporated into micelles, and consequently, the monomer concentration is kept almost constant. Thus, micelles act as a peptide reservoir. Micelles are located on-pathway, since they serves as nucleation centers. Experimental data support the model, since above 17.7 microM the time of half-aggregation is independent of peptide concentration, and the overall reaction of the conversion of monomer peptide into fibril can be treated as an apparent first-order reaction.
阿尔茨海默病（AD）的特征是由β-淀粉样蛋白（Aβ）肽形成的纤维状沉积物的沉积。最被广泛接受的Aβ纤维形成模型认为，纤维形成发生在两个不同阶段，即成核和延伸。该模型的一种修正包括胶束的形成。我们通过精确的实验测定证明了具有胶束性质的聚集体的存在（即临界胶束浓度，CMC，和聚集数）。CMC值分别通过表面张力分析（17.5微摩尔）和芘荧光变化（17.6微摩尔）获得。通过荧光猝灭测定的平均聚集数为25，且与肽浓度无关。胶束的存在意味着在CMC以上，所有过量的肽都被纳入胶束中，因此，单体浓度几乎保持恒定。因此，胶束充当肽库。胶束位于反应途径上，因为它们作为成核中心。实验数据支持该模型，因为在17.7微摩尔以上，半聚集时间与肽浓度无关，并且单体肽转化为纤维的整体反应可以被视为表观一级反应。
