IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
LYSOZYME AMYLOIDOGENESIS IN VITRO IS DELAYED BY ITS NATURAL ACTIVITY INHIBITORS
Autor/es:
RODRIGO PAGANO; MÁXIMO LÓPEZ MEDUS; ANA VILLAMIL GIRALDO; ARMANDO J. PARODI; JULIO CARAMELO
Lugar:
Tucumán-Argentina
Reunión:
Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009
Institución organizadora:
SAIB
Resumen:
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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)