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2025-01-01
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- IOC - Artigos de Periódicos [12776]
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SMALL MOLECULE INHIBITORS OF LYSOZYME AMYLOID AGGREGATION
Peptídeo β-amilóide
Lisozima clara de ovo de galinha
Amiloidose sistêmica
Author
Affilliation
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Bioquímica e Biofísica Celular. Rio de Janeiro, RJ, Brasil.
Instituto Militar de Engenharia. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultraestrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Bioquímica e Biofísica Celular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Bioquímica e Biofísica Celular. Rio de Janeiro, RJ, Brasil.
Instituto Militar de Engenharia. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultraestrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Bioquímica e Biofísica Celular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Bioquímica e Biofísica Celular. Rio de Janeiro, RJ, Brasil.
Abstract
Protein amyloid aggregation is associated with a number of important human pathologies, but the precise
mechanisms underlying the toxicity of amyloid aggregates are still incompletely understood. In this context,
drugs capable of blocking or interfering with the aggregation of amyloidogenic proteins should be considered
in strategies aimed at the development of novel therapeutic agents. Human lysozyme variants have been shown
to form massive amyloid deposits in the livers and kidneys of individuals affected by hereditary systemic amyloidosis.
Currently, there are no clinical treatments available to prevent or reverse formation of such amyloid
deposits. We have recently described a number of di- and trisubstituted aromatic compounds that block the formation
of soluble oligomers and amyloid fibrils of the β-amyloid peptide (Aβ) and protect hippocampal neurons
in culture from Aβ-induced toxicity. Here, we show that some of those compounds inhibit the formation
and disrupt preformed amyloid fibrils from both human and hen egg white lysozyme. These results suggest that
these small molecule compounds may serve as prototypes for the development of drugs for the prevention or
treatment of different types of amyloidoses.
Keywords in Portuguese
Agregação de proteínas amilóidesPeptídeo β-amilóide
Lisozima clara de ovo de galinha
Amiloidose sistêmica
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