Interactions of recombinant prions with compounds of therapeutical significance.

Biochem Biophys Res Commun

University of Hamburg, Department of Biochemistry and Molecular Biology, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.

Published: June 2006

AI Article Synopsis

  • The study focuses on preventing the transformation of the normal prion protein (PrP(C)) into its infectious form (PrP(Sc)), which leads to fatal brain diseases.
  • Researchers tested several therapeutic agents that inhibit the formation and accumulation of the infectious prion, showing that these compounds promote a higher alpha-helical content in prion aggregates and eliminate the typical beta-structure seen in PrP(Sc).
  • The findings suggest that enhancing alpha-helix formation and preventing beta-sheet structure may offer a way to resist the harmful transformation of PrP(C) into PrP(Sc), potentially paving the way for treatments for neurodegenerative diseases.

Article Abstract

The transformation of the cellular prion protein (PrP(C)) into the infectious form (PrP(Sc)) is implicated in the invariably fatal transmissible spongiform encephalopathies. To identify a mechanism to prevent the undesired PrP(C)-->PrP(Sc) transformation, we investigated the interactions of recombinant prion proteins with a number of potential therapeutic agents which inhibit the PrP(Sc) formation, infectivity, and the accumulation of the misfolded form. We show that the prion aggregates formed in the presence of six compounds have no beta-structure, which is typical of the infectious form, and possess considerably higher alpha-helical content than the normal PrP(C). The investigated compounds stimulate the formation of alpha-helices and the destruction of beta-structure. They prevent the transformation of alpha-helical structure into beta-sheets. Probably, this is the reason for the resistance to PrP(C)-->PrP(Sc) transformation in the presence of these compounds. The results may be useful for the future therapy of neurodegenerative diseases.

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http://dx.doi.org/10.1016/j.bbrc.2006.03.135DOI Listing

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