C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis

Faravelli, G., Raimondi, S., Marchese, L., Partridge, F.A., Soria, C., Mangione, P.P., Canetti, D., Perni, M., Aprile, F.A., Zorzoli, I., Di Schiavi, E., Lomas, D.A., Bellotti, V., Sattelle, D.B. and Giorgetti, S. 2019. C. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis. Scientific Reports. 9 19960. https://doi.org/10.1038/s41598-019-56498-5

TitleC. elegans expressing D76N β2-microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis
TypeJournal article
AuthorsFaravelli, G., Raimondi, S., Marchese, L., Partridge, F.A., Soria, C., Mangione, P.P., Canetti, D., Perni, M., Aprile, F.A., Zorzoli, I., Di Schiavi, E., Lomas, D.A., Bellotti, V., Sattelle, D.B. and Giorgetti, S.
Abstract

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.

Article number19960
JournalScientific Reports
Journal citation9
ISSN2045-2322
Year2019
PublisherNature Publishing Group
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1038/s41598-019-56498-5
Web address (URL)https://doi.org/10.1038/s41598-019-56498-5
Publication dates
Published27 Dec 2019

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