Imperial College London
Portrait Picture

Dr Francesco A. Aprile

Faculty of Natural Sciences, Department of Chemistry

Lecturer in Chemistry
 
 
 
//

Contact

 

+44 (0)20 7594 5545f.aprile Website

 
 
//

Location

 

110FMolecular Sciences Research HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Faravelli:2019:10.1038/s41598-019-56498-5,
author = {Faravelli, G and Raimondi, S and Marchese, L and Partridge, FA and Soria, C and Mangione, PP and Canetti, D and Perni, M and Aprile, FA and Zorzoli, I and Di, Schiavi E and Lomas, DA and Bellotti, V and Sattelle, DB and Giorgetti, S},
doi = {10.1038/s41598-019-56498-5},
journal = {Sci Rep},
title = {C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis.},
url = {http://dx.doi.org/10.1038/s41598-019-56498-5},
volume = {9},
year = {2019}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The availability of a genetic model organism with which to study key molecular events underlying amyloidogenesis is crucial for elucidating the mechanism of the disease and the exploration of new therapeutic avenues. The natural human variant of β2-microglobulin (D76N β2-m) is associated with a fatal familial form of systemic amyloidosis. Hitherto, no animal model has been available for studying in vivo the pathogenicity of this protein. We have established a transgenic C. elegans line, expressing the human D76N β2-m variant. Using the INVertebrate Automated Phenotyping Platform (INVAPP) and the algorithm Paragon, we were able to detect growth and motility impairment in D76N β2-m expressing worms. We also demonstrated the specificity of the β2-m variant in determining the pathological phenotype by rescuing the wild type phenotype when β2-m expression was inhibited by RNA interference (RNAi). Using this model, we have confirmed the efficacy of doxycycline, an inhibitor of the aggregation of amyloidogenic proteins, in rescuing the phenotype. In future, this C. elegans model, in conjunction with the INVAPP/Paragon system, offers the prospect of high-throughput chemical screening in the search for new drug candidates.
AU  - Faravelli,G
AU  - Raimondi,S
AU  - Marchese,L
AU  - Partridge,FA
AU  - Soria,C
AU  - Mangione,PP
AU  - Canetti,D
AU  - Perni,M
AU  - Aprile,FA
AU  - Zorzoli,I
AU  - Di,Schiavi E
AU  - Lomas,DA
AU  - Bellotti,V
AU  - Sattelle,DB
AU  - Giorgetti,S
DO  - 10.1038/s41598-019-56498-5
PY  - 2019///
TI  - C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis.
T2  - Sci Rep
UR  - http://dx.doi.org/10.1038/s41598-019-56498-5
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31882874
VL  - 9
ER  -
Download