Pharmacologic approaches in the treatment of familial amyloidotic polyneuropathy [Utilização de fármacos na terapia da polineuropatia amiloidótica familiar]

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Damas, AM (Author) Other; Almeida, MR (Author) ICBAS; Gales, L (Author) ICBAS; Cardoso, I (Author) Other; Saraiva, MJ (Author) Other

Journal

Title: Sinapse

Vol. 6

Pages: 168-173

ISSN: 1645-281X

Publisher: Sociedade Portuguesa de Neurologia

Indexing

ISI Web of Knowledge

Scopus - 1 Citation

Other information

Authenticus ID: P-007-FRQ

Abstract (EN): In Familial Amyloidotic Polyneuropathy, Portuguese type, a transthyretin variant, TTR V30M forms amyloid fibrils which deposit extracellularly. More than eighty TTR variants are known, most of them being pathogenic. The mechanism of TTR fibril formation is still not completely elucidated. However it is widely accepted that the amino acid substitutions in the TTR variants contribute to a destabilizing effect on the TTR tetramer molecule, which in particular conditions dissociate into non native monomeric intermediates that aggregate and polymerize in amyloid fibrils that further elongate. Since this is a multi-step process there is the possibility to impair TTR amyloid fibril formation at different stages of the process namely by tetramer stabilization, inhibition of fibril formation or fibril disruption. Until now the only efficient therapy available is liver transplant when performed in an early phase of the onset of the disease symptoms. Since this is a very invasive therapy alternatives are desirable. In that sense, several compounds have been proposed to impair amyloid formation or disruption. Based on the proposed mechanism for TTR amyloid fibril formation we discuss the action of some of the proposed TTR stabilizers and the action of amyloid disrupters.

Language: Portuguese

Type (Professor's evaluation): Scientific