UCL Institute of Neurology

A new model of prion disease may represent a paradigm shift in the mechanisms thought to underlie these infectious, neurodegenerative disorders.

Prion diseases, such as Creutzfeldt–Jacob disease, have a clinically silent incubation period that can go on for years or decades, followed by an aggressive, short clinical phase.

The new model, based on mouse studies, indicates that the spread of prions in the brain occurs in two distinct phases. In the first, longer, clinically silent phase, non-neurotoxic prions multiply exponentially until a defined limit is reached. Then the second, shorter plateau phase sees the amassed prions catalyse the formation of toxic prion particles. And whereas the length of the infectious phase is not dependent on prion concentration, the time it takes for the mouse to succumb after the plateau of infectivity is reached is inversely correlated with the amount of prion protein that it produces.

The model, proposed by John Collinge and colleagues from the IoN Department of Neurodegenerative Disease, and the MRC Prion Unit  in this week's Nature, hints that prion infectivity and toxicity are separate processes and, remarkably, that infectious and toxic particles may not be the same.

reference >> Prion propagation and toxicity in vivo occur in two distinct mechanistic phases

Malin K. Sandberg, Huda Al-Doujaily, Bernadette Sharps, Anthony R. Clarke & John Collinge
Nature 2011: 470, 540–542

read more >> MRC Prion Unit | IoN Department of Neurodegenerative Disease

Text courtesy of Nature