Support for the multigenic hypothesis of amyloidosis: The binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influencestransthyretin amyloidogenicity in vitro

Citation
Jt. White et Jw. Kelly, Support for the multigenic hypothesis of amyloidosis: The binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influencestransthyretin amyloidogenicity in vitro, P NAS US, 98(23), 2001, pp. 13019-13024
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
98
Issue
23
Year of publication
2001
Pages
13019 - 13024
Database
ISI
SICI code
0027-8424(20011106)98:23<13019:SFTMHO>2.0.ZU;2-D
Abstract
The amyloidoses are a large group of protein misfolding diseases. Genetic a nd biochemical evidence support the hypothesis that amyloid formation from wild-type or 1 of 80 sequence variants of transthyretin causes the human am yloid diseases senile systemic amyloidosis or familial amyloid polyneuropat hy, respectively. The late onset and variable penetrance of these diseases has led to their designation as multigenic-implying that the expression lev els and alleles of multiple gene products influence the course of pathology . Here we show that the binding stoichiometry of three interacting molecule s, retinol-binding protein, vitamin A, and L-thyroxine, notably influenced transthyretin amyloidogenicity in vitro. At least 70 genes control retinol- binding protein, vitamin A, and L-thyroxine levels in plasma and have the p otential to modulate the course of senile systemic amyloidosis or familial amyloid polyneuropathy.