Prions

07 Oct, 2024

Prions are a type of small protein / peptide that is capable of causing disease through inducing misfolding of native proteins, leading to cell death. They can lead to brain damage, and pathologies can take several years to develop.¹ Prion diseases always lead to the death of the infected individual, and there are no existing treatments or vaccinations. ¹ Prions are highly resistant to a range of environmental conditions, including acidic stomachs and freezing temperatures. One method of transmission is the faecal-oral route in deer populations.²

BSE, mad cow disease, is a well known prion disease. In the mid-1980s, the UK had an outbreak of BSE resulting in the infection of millions of cows.

Prion disease may also be called transmissible spongiform encephalopathies (TSE),³ and do not reliably elicit an immune response from the host. Although it is not fully understood, it is thought that the accumulation of disease-associated prion in neurons causes damage to the nervous system, reducing the protective effect of the healthy prion protein.³

Prions can interfere with cell’s ability to clear misfolded protein, leading to aggregation and subsequent death.⁴ Once an infectious prion is present, it can induce misfolding in other prion proteins and cause more aggregation within the cell. This then leads to neuronal damage. Prions contradict the theory that nucleic acids must be present for an infectious disease.

Other proteins found to be involved in neurodegenerative diseases like Alzheimer’s, Huntington’s, and Parkinson’s have similar modes of action to prions. It has not yet been demonstrated if these conditions are transmissible through the introduction of disease-associated prion into healthy subjects.²

Potential treatments of prion diseases could include blocking the synthesis of disease-associated protein, through the use of antisense oligonucleotides or RNAi.⁵,⁶ Antibodies and hypochlorous acid (which isn’t toxic to humans) have also been used successfully to target prions. Animal models have demonstrated these therapeutics can prolong life when used soon after infection - this is problematic as symptoms do not usually manifest until months or years after the initial infection (in the case of BSE, it can be 20 years before the first symptoms present).⁷

Assays, such as the Real Time-Quaking Induced Conversion (RT-QuIC) assay, can be used to detect misshapen proteins, amplifying undetectable levels of protein. This assay is used to diagnose Alzheimer’s, Parkinson’s, some forms of Dementia, and other neurological conditions that involve misfolded proteins.⁷