Anti-apoptotic treatment reduces transthyretin deposition in a transgenic mouse model of Familial Amyloidotic Polyneuropathy

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Barbara Macedo (Autor) Outra; Ana Rita Batista (Autor) Outra; Nelson Ferreira (Autor) Outra; Maria Rosario Almeida (Autor) ICBAS; Maria Joao Saraiva (Autor) ICBAS

Revista

Título: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1782

Páginas: 517-522

ISSN: 0925-4439

Editora: Elsevier

Indexação

ISI Web of Knowledge - 52 Citações

Scopus - 59 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

Outras Informações

ID Authenticus: P-003-WCC

DOI: 10.1016/j.bbadis.2008.05.005

Abstract (EN): Tauroursodeoxycholic acid (TUDCA) is a unique natural compound that acts as a potent anti-apoptotic and anti-oxidant agent, reducing cytotoxicity in several neurodegenerative diseases. Since oxidative stress, apoptosis and inflammation are associated with transthyretin (TTR) deposition in Familial Amyloidotic Polyneuropathy (FAP), we investigated the possible TUDCA therapeutical application in this disease. We show by semi-quantitative immunohistochemistry and western blotting that administration of TUDCA to a transgenic mouse model of FAP decreased apoptotic and oxidative biomarkers usually associated with TTR deposition, namely the ER stress markets BiP and eIF2 alpha, the Fas death receptor and oxidation products such as 3-nitrotyrosine. Most important, TUDCA treatment significantly reduced TTR toxic aggregates in as much as 75%. Since TUDCA has no effect on TTR aggregation "in vitro", this finding points for the "in vivo" modulation of TTR aggregation by cellular responses, such as by oxidative stress, ER stress and apoptosis and prompts for the use of this safe drug in prophylactic and therapeutic measures in FAR

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6