Highly infectious prions are not directly neurotoxic.

Proceedings of the National Academy of Sciences of the United States of America (2020-09-10)
Iryna Benilova, Madeleine Reilly, Cassandra Terry, Adam Wenborn, Christian Schmidt, Aline T Marinho, Emmanuel Risse, Huda Al-Doujaily, Michael Wiggins De Oliveira, Malin K Sandberg, Jonathan D F Wadsworth, Parmjit S Jat, John Collinge

Prions are infectious agents which cause rapidly lethal neurodegenerative diseases in humans and animals following long, clinically silent incubation periods. They are composed of multichain assemblies of misfolded cellular prion protein. While it has long been assumed that prions are themselves neurotoxic, recent development of methods to obtain exceptionally pure prions from mouse brain with maintained strain characteristics, and in which defined structures-paired rod-like double helical fibers-can be definitively correlated with infectivity, allowed a direct test of this assertion. Here we report that while brain homogenates from symptomatic prion-infected mice are highly toxic to cultured neurons, exceptionally pure intact high-titer infectious prions are not directly neurotoxic. We further show that treatment of brain homogenates from prion-infected mice with sodium lauroylsarcosine destroys toxicity without diminishing infectivity. This is consistent with models in which prion propagation and toxicity can be mechanistically uncoupled.

Product Number
Product Description

Anti-Spinophilin/Neurabin-II Antibody, Upstate®, from rabbit
N-Lauroylsarcosine sodium salt, BioUltra, for molecular biology, ≥99.0% (HPLC)
Anti-NeuN Antibody, clone A60, Alexa Fluor 555 Conjugate, clone A60, from mouse, ALEXA FLUOR 555