According to a study published in the online edition of the journal Proceedings of the National Academy of Sciences, a single prion protein that is at least 10 times more lethal than larger prion species has been identified by researchers from The Scripps Research Institute. The single prion protein causes neuronal death similar to that observed in BSE (mad cow disease).
This toxic single molecule or “monomer” tests the existing theory that neuronal damage is associated with the toxicity of prion protein aggregates called “oligomers.”
Scripps Florida Professor Corinne Lasmézas, who led the study, explained:
“By identifying a single molecule as the most toxic species of prion proteins, we’ve opened a new chapter in understanding how prion-induced neurodegeneration occurs. We didn’t think we would find neuronal death from this toxic monomer so close to what normally happens in the disease state. Now we have a powerful tool to explore the mechanisms of neurodegeneration.”
The researchers discovered that the toxic form of abnormal prion protein, known as TPrP, triggered various forms of neuronal damage, ranging from molecular signatures very similar to that seen in the brains of prion-infected animals, autophagy – the self-eating of cellular components, and apoptosis – programed cell death. The team found that the most lethal form of prion protein was a specific structure known as alpha-helical.
The new study provides fresh insights into prion diseases, such as BSE and a rare human form Creutzfeldt-Jakob disease. Furthermore, it opens the possibility that associated neurotoxic proteins may play a role in neurodegenerative disorders, such as Parkinson, and Alzheimer’s diseases.
In prion disease, proteianceous infectious particles (infectious prions), believed to be made up only of protein, are able to reproduce, even though they lack RNA and DNA. Usually, mammalian cells generate cellular prion protein (PrP), when infected with a prion disease, the abnormal protein converts the normal host prion protein into its disease form.
Prion diseases are similar to other protein misfolding diseases, such as Alzheimer’s, because they are triggered by the toxicity of a misfolded host protein. In addition, a recent study published in The New York Times, discovered that diseases, such as Alzheimer’s, mirror prion disease by spreading from cell to cell.
“Until now, it was thought that oligomers of proteins are toxic in all these disease. Since we found for the first time that an abnormally folded monomer is highly toxic, it opens up the possibility that this might be true also for some other protein misfolding diseases as well.”
Written by Grace Rattue