- Normal proteinEveryone makes prion protein. It sits on the surface of cells.
- A wrong foldSome of the protein folds into the wrong shape.
- It spreads its shapeThe misfolded form causes more protein to misfold.
- Build-upMisfolded protein gathers and is hard to clear.
- Nerve cells are damagedThis causes the symptoms of the illness.
Mechanism research asks how a misfolded protein spreads, why it takes different forms, and how it damages neurons. Active groups frame the questions in similar terms. The PRIONS team at the IHAP unit in Toulouse, led by Olivier Andreoletti with Tomas Barrio as co-leader and nine listed members, works on three themes: plasticity of prion strains, transmission within and between species, and the pathogenesis of transmissible spongiform encephalopathies. It also applies prion mechanisms to prion-like diseases such as Parkinson disease, Alzheimer disease and amyotrophic lateral sclerosis.
Mechanisms also explain practical measures. A 2013 pooled analysis of more than 200 studies by member companies of the Plasma Protein Therapeutics Association found good agreement between groups on prion removal by manufacturing steps, and the steps with the highest removal were those where prions and the therapeutic protein differ most in physical and chemical behaviour. Start with the overview, then protein misfolding, strains, the species barrier, neurotoxicity and PrP function. Related pages are genetics, open questions and the Research hub.
Explore
- How prions damage neuronsWhat is known and unresolved about how prions kill neurons: candidate toxic species, the requirement for PrPC, synaptic loss and stress pathways.
- What are prion diseases?: researchPrion diseases as a disease class: incidence, the sporadic, genetic and acquired categories, molecular subtypes, and what the classification does not yet resolve.
- What is a prion?: researchWhat a prion is in structural terms: PrP conformers, seeded polymerisation, the PIRIBS fibril architecture from cryo-EM, and the gaps that remain.
- Normal function of PrPWhat a 2017 review concludes about the normal function of cellular prion protein: myelin maintenance is best supported, several older proposals are doubted.
- Prion strainsWhat prion strains are, how they are distinguished, what cryo-EM shows about two laboratory strains, and which questions about strains remain open.