Luminescent conjugated polymers
 Read with caution! This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk. |
The Internet is awfully excited about luminescent conjugated polymers! “Prions eliminated,” they say. “First treatment for prion-based disease.”
While that may be premature, LCPs have apparently been shown to decrease infectivity of prion-infected brain slices, and to decrease concentration of PrP(Sc) oligomers in an avidity assay. They seem to do this by stabilizing PrP aggregates — perhaps so toxic oligomers are less likely to break off? Authors include Adriano Aguzzi, among others.
Still working on understanding what a luminescent conjugated polymer is and how it works. Abstract from the paper, published on April 6th, here and below.
Capsule
Background: Luminescent conjugated polymers (LCPs) are highly specific to amyloid conformations and may represent potential antiprion compounds.
Results: LCPs significantly reduce prion titers, while rendering PrPSc more stable to proteolytic digestion.
Conclusion: LCPs possess pronounced antiprion potential and appear to act by compaction of frangible fibers.
Significance: LCPs may represent novel pharmacophores for the prevention and treatment of prion diseases.
Abstract
LCPs interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here we show that a variety of anionic, cationic and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices COCS, and decreased the amount of PrPSc oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, and triggered the compaction and enhanced the resistance to proteolysis of recombinant mPrP23-231 fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on COCS and in vitro conversion assays with mPrP23-231 indicated that PTAA may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.