[13] The structural stability of prions makes them resistant to denaturation by chemical or physical agents, complicating disposal and containment, and raising concerns about iatrogenic spread through medical instruments.

The PrP found in infectious prions has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins.

[21] PrPC is a normal protein found on the membranes of cells, "including several blood components of which platelets constitute the largest reservoir in humans.

[29] PrPC is readily digested by proteinase K and can be liberated from the cell surface by the enzyme phosphoinositide phospholipase C (PI-PLC), which cleaves the glycophosphatidylinositol (GPI) glycolipid anchor.

[40] In the prion amyloids, the glycolipid anchors and asparagine-linked glycans, when present, project outward from the lateral surfaces of the fiber cores.

[36] Different prion strains have distinct templates, or conformations, even when composed of PrP molecules of the same amino acid sequence, as occurs in a particular host genotype.

[46] Protease-resistant PrPSc-like protein (PrPres) is the name given to any isoform of PrPc which is structurally altered and converted into a misfolded proteinase K-resistant form.

[47] To model conversion of PrPC to PrPSc in vitro, Kocisko et al. showed that PrPSc could cause PrPC to convert to PrPres under cell-free conditions [48] and Soto et al. demonstrated sustained amplification of PrPres and prion infectivity by a procedure involving cyclic amplification of protein misfolding.

While data from in vitro experiments suggest many dissimilar roles, studies on PrP knockout mice have provided only limited information because these animals exhibit only minor abnormalities.

[53] As well, a 2004 study found that mice lacking genes for normal cellular PrP protein show altered hippocampal long-term potentiation.

[56] A 2006 article from the Whitehead Institute for Biomedical Research indicates that PrP expression on stem cells is necessary for an organism's self-renewal of bone marrow.

Manfred Eigen showed that the heterodimer model requires PrPSc to be an extraordinarily effective catalyst, increasing the rate of the conversion reaction by a factor of around 1015.

[60] This problem does not arise if PrPSc exists only in aggregated forms such as amyloid, where cooperativity may act as a barrier to spontaneous conversion.

[66] The incubation period is determined by the exponential growth rate, and in vivo data on prion diseases in transgenic mice match this prediction.

[69][70] Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloids, which disrupt the normal tissue structure.

[78] Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes.

[90] Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived human menopausal gonadotropin, administered for the treatment of infertility, was published in 2011.

Genetic research has identified an association between susceptibility to sCJD and a polymorphism at codon 129 in the PRNP gene, which encodes the prion protein (PrP).

[96] The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions: 134 °C (273 °F) for 18 minutes in a pressurized steam autoclave has been found to be somewhat effective in deactivating the agent of disease.

[108] More recent studies suggest scrapie prions can be degraded by diverse cellular machinery of the affected animal cell.

[120] All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets.

[66] Fungal proteins exhibiting templated conformational change[further explanation needed] were discovered in the yeast Saccharomyces cerevisiae by Reed Wickner in the early 1990s.

[121] There is evidence that fungal proteins have evolved specific functions that are beneficial to the microorganism that enhance their ability to adapt to their diverse environments.

[133] The pathogenicity of prions and proteins with prion-like domains is hypothesized to arise from their self-templating ability and the resulting exponential growth of amyloid fibrils.

[128] Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration.

The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation.

This disease caused the affected animals to "lie down, bite at their feet and legs, rub their backs against posts, fail to thrive, stop feeding and finally become lame".

During the 1960s, two London-based researchers, radiation biologist Tikvah Alper and biophysicist John Stanley Griffith, developed the hypothesis that the transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins.

Field into scrapie and kuru had found evidence for the transfer of pathologically inert polysaccharides that only become infectious post-transfer, in the new host.

[148] The revised hypothesis was later formulated, in part, to accommodate reverse transcription (which both Howard Temin and David Baltimore discovered in 1970).