Review: TTR amyloidosis - Structural features leading to protein aggregation and their implications on therapeutic strategies

Citation
Am. Damas et Mj. Saraiva, Review: TTR amyloidosis - Structural features leading to protein aggregation and their implications on therapeutic strategies, J STRUCT B, 130(2-3), 2000, pp. 290-299
Citations number
71
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF STRUCTURAL BIOLOGY
ISSN journal
1047-8477 → ACNP
Volume
130
Issue
2-3
Year of publication
2000
Pages
290 - 299
Database
ISI
SICI code
1047-8477(200006)130:2-3<290:RTA-SF>2.0.ZU;2-9
Abstract
Transthyretin amyloidosis represents a spectrum of clinical syndromes that, in all cases except senile systemic amyloidosis, are dependent on the muta tion present in the transthyretin (TTR) protein. Although the role of amylo id deposits in the pathogenesis of the disease is not clear, preventing the ir formation or promoting their disaggregation is necessary to control the development of clinical symptoms. The design of therapies aiming at prevent ing amyloid formation or promoting its dissociation requires detailed knowl edge of the fibrils' molecular structure and a complete view about the fact ors responsible for protein aggregation. This review is focused on the stru ctural studies, performed on amyloid fibrils and amyloidogenic TTR variants , aiming at understanding the aggregation mechanism as well as the atomic s tructure of the fibril assembly, Based on the available information possibl e therapies are also surveyed. (C) 2000 Academic Press.