title: Charge regulation phenomenon predicted from the modeling of polypeptide electrophoretic mobilities as a relevant mechanism of amyloid-beta peptide oligomerization.
abstract: Electrophoretic mobilities of amyloid-beta (1-40) and (1-42) peptides and their aggregates are modeled to study the amyloidogenic pathway associated with Alzheimer´s Disease. The near molecule pH generated by the intraparticle charge regulation phenomenon during the oligomerization of amyloid-beta (1-40) and (1-42) peptides is evaluated and discussed as a relevant mechanism supporting the "amyloid cascade hypothesis" proposed in the literature. A theoretical framework associated with the oligomerization of amyloid-beta peptides including simple scaling laws and the consideration of electrokinetic and hydrodynamic global properties of oligomers is presented. The central finding is the explanation of the near molecule pH change toward the pI when the oligomerization number increases. These results allow one to rationalize consecutive physical stages that validate the amyloid cascade hypothesis. Concluding remarks involving mainly the effects of pair and intraparticle charge regulation phenomena on the amyloidogenic pathway with some suggestions for future research are provided.
authors.affiliation: Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), Universidad Nacional del Litoral (UNL), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Deiber
authors.affiliation: Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), Universidad Nacional del Litoral (UNL), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina.
authors.forename: Marta B
authors.initials: MB
authors.lastname: Peirotti
authors.affiliation: Cátedra de Bioquímica Básica de Macromoléculas, Facultad de Bioquímica y Ciencias Biológicas, UNL, Santa Fe, Argentina.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Piaggio
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D019075:Electrophoresis, Capillary / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D058105:Polymerization
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments
keywords: Amyloid cascade hypothesis; Amyloid-beta peptides; Charge regulation phenomenon; Electrophoretic mobility; Peptide oligomerization