Targeting The Ribosome For Antiprion Medicines
Prion diseases are fatal neurodegenerative diseases caused by misfolding of prion proteins. Examples of prion diseases are scrapie in sheep, mad cow disease and Creutzfeldt-Jakob disease in human.
What triggers misfolding of the prion proteins to the amyloid disease form is an open question. The inadequate knowledge in the field about the factors involved in prion formation makes the discovery of effective medicines for prion diseases rather challenging.
"We have now shown that the protein folding activity of the ribosome (PFAR) is most likely involved in prion propagation and thus, can be a specific target for antiprion medicines. If we understand the mechanism fully, we will be able to find ways to stop that too.", says Suparna Sanyal, senior lecturer at the Department of Cell and Molecular Biology, Uppsala University .
The ribosome is the protein synthesis machinery of the cell. The mechanism of protein synthesis by the ribosome is well characterized, while PFAR is a rather recent discovery. PFAR is a ribosomal RNA dependent function of the large subunit of the ribosome irrespective of its source. The PFAR center closely overlaps the peptidyl transferase center although the nucleobases responsible for these two functions are not all common.
"Our results show that two prion inhibitors 6-aminophenanthridine and guanabenz acetate implement antiprion activity by binding to ribosomal RNA and inhibiting PFAR. Thus, the ribosome and more specifically PFAR is the new target for antiprion medicines. Furthermore, we have developed an in vitro PFAR assay, which can be used as a platform for screening prion inhibitors in a high-throughput fashion. This assay is much more time and cost-effective than standard prion assays", says Suparna Sanyal.
Reference: Pang, Y., Kurella, S., Voisset, C., Samanta, D., Banerjee, D., Schabe, A., Dasgupta, C., Galons, H., Blondel, M., and Sanyal, S. (2013) The antiprion compound 6-Aminophenanthridine inhibits protein folding activity of the ribosome by direct competition. J. Biol. Chem. doi/10.1074/jbc.M113.466748
Source: EurekAlert!, the online, global news service operated by AAAS, the science society
Please use one of the following formats to cite this article in your essay, paper or report:
Uppsala University. "Targeting The Ribosome For Antiprion Medicines." Medical News Today. MediLexicon, Intl., 5 Jul. 2013. Web.
27 May. 2017. <http://www.medicalnewstoday.com/releases/262845.php>
Uppsala University. (2013, July 5). "Targeting The Ribosome For Antiprion Medicines." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
Contact our news editors
For any corrections of factual information, or to contact our editorial team, please see our contact page.
Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.