CONICET | Buscador de Institutos y Recursos Humanos

LYSOZYME AMYLOIDOGENESIS IN VITRO IS DELAYED BY ITS NATURAL ACTIVITY INHIBITORS Pagano RS, López Medus M, Villamil Giraldo A, Parodi AJ, Caramelo JJ. Fundación Instituto Leloir, Patricias Argentinas 435, C1405 Buenos Aires, Argentina Several proteins can fold abnormally in vivo and have the capacity of forming fibrils, aggregates 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 characteristics with many neurodegenerative diseases as Parkinson, 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 or 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 inhibitors (N-acetyl glucosamine, N-acetyl chitobiose and N-acetyl chitotriose) hinder amyloid formation in vitro and that this fibril-growth inhibition correlates with ligand concentration and their affinities for LYZ. These results have been corroborated in the present study. Besides aggregates formed by Guanidinium Hydrochloride destabilization of LYZ in this work proved to have amyloid fibril characteristics by Atomic Force Microscopy (AFM)