Lysozyme amyloidogenesis in vitro is delayed by its natural activity inhibitors

PAGANO, RODRIGO SEBASTIÁN; LÓPEZ MEDUS, MÁXIMO; VILLAMIL GIRALDO, ANA; PARODI, ARMANDO JOSÉ; CARAMELO, JULIO JAVIER

San Miguel de Tucumán, Tucumán, Argentina

Congreso; Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Several proteins can fold abnormally in vivo and have the capacity of forming fibrils, agregates and deposits. The diseases linked to massive deposits of fibrillar aggregates are known as amyloidosis, and those formed by aggregation of misfolded LYZ share common charecterists with many neurodegenerative diseases as Prkinson, Alzheimer and Transmissible Spongiform Encephalopathies (TSEs). The mechanisms that determine how amyloidogenic proteins form oligomers and fibrils and why they  are toxic are still elusive. Lysozyme (LYZ) is one of the most intensively used experimental models of amyloid formation. Two main approaches have been employed in order to delay or restrain their formation: fibril breaking of protein native state stabilization. Since the most cytotoxic species seem to be the oligomeric forms, we followed the latter strategy. We have previously shown that the stabilization of the native state of the Lyz by its natural activity inhbitos(N-acetyl glucosamine, N-acetyl chitobiose and N-acetyl chitotriose) amyloid formation in vitro and that this fibril-growth inhibition correlates with ligand concentration and theri affinities for LYZ. These results have been corroborated in the present study. Besides aggregates fomed by Guanidinium HYdrochloride destabilization of LYZ in this work proved to have amyloid fibril characteristics by Atomic Force Microscopy(AFM).