True and apparent inhibition of amyloid fibril formation

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Pedro M. Martins (Author) FEUP

Journal

Title: Prion

Vol. 7 No. 2

Pages: 136-139

ISSN: 1933-6896

Publisher: Taylor & Francis

Indexing

ISI Web of Science

Scopus

Associated Projects

PTDC/BIA-PRO/101260/2008 - Crescimento de Cristais de Proteínas com Propriedades de Difracção de Raios-X de Elevada Qualidade

Other information

DOI: 10.4161/pri.23111

Abstract (EN): A possible therapeutic strategy for amyloid diseases involves the use of small molecule compounds to inhibit protein assembly into insoluble aggregates. According to the recently proposed crystallization-like model, the kinetics of amyloid fibrillization can be retarded by decreasing the frequency of new fibril formation or by decreasing the elongation rate of existing fibrils. To the compounds that affect the nucleation and/or the growth steps we call true inhibitors. An apparent inhibition mechanism may however result from the alteration of thermodynamic properties such as the solubility of the amyloidogenic protein. Apparent inhibitors markedly influence protein aggregation kinetics measured in vitro, yet they are likely to lead to disappointing results when tested in vivo. This is because cells and tissues media are in general much more buffered against small variations in composition than the solutions prepared in lab. Here we show how to discriminate between true and apparent inhibition mechanisms from experimental data on protein aggregation kinetics. The goal is to be able to identify false positives much earlier during the drug development process.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 4