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

• Type: Article in International Scientific Journal
• Date: 2008

Authors

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

Journal

Title: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1782

Pages: 517-522

ISSN: 0925-4439

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 59 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: 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

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6