Prions: Videos & Practice Problems

Prions, short for proteinaceous infectious agents, are unique pathogens that differ significantly from viruses and viroids. Unlike viruses, which consist of proteins, nucleic acids, and sometimes lipids, prions are solely composed of misfolded proteins. This misfolding is critical, as prions can induce normal proteins in the brain to also misfold, leading to severe neurodegenerative diseases.

Some notable prion diseases in humans include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru. In animals, prion diseases manifest as scrapie, mad cow disease (bovine spongiform encephalopathy), and chronic wasting disease. The accumulation of these misfolded proteins in neural tissue results in transmissible spongiform encephalopathies (TSEs), characterized by the degeneration of brain tissue that creates a sponge-like appearance due to the formation of holes or lesions.

When comparing healthy brain tissue to that affected by spongiform encephalopathies, the differences are stark. Healthy brain cells appear intact, while those affected by TSEs show significant deterioration, with numerous gaps that contribute to the spongiform texture. This degeneration is directly linked to the presence of prions and underscores the serious implications of prion diseases on both human and animal health.

Understanding prions and their mechanisms is crucial as we delve deeper into their impact on neurodegenerative diseases in future discussions.

Prion diseases, such as scrapie in animals, are caused by misfolded proteins known as prions. The infectious form of the prion protein is referred to as PrP_Sc, which stands for prion protein scrapie, while the normal, non-infectious form is called PrP_C, or prion protein cellular. The critical aspect of prion pathology lies in the interaction between these two forms of the protein.

When PrP_Sc comes into contact with PrP_C, it induces a conformational change in the normal protein, causing it to misfold into the infectious form. This process leads to the accumulation of PrP_Sc in the brain, which aggregates and forms clumps. Over time, these aggregates result in spongiform encephalitis, characterized by the formation of sponge-like lesions in brain tissue.

Inside neurons, the presence of both PrP_C and PrP_Sc can initiate a chain reaction where the misfolded prion protein converts more normal proteins into the pathogenic form. This accumulation and aggregation of PrP_Sc disrupt normal cellular function and lead to severe neurological damage, ultimately resulting in the clinical manifestations of scrapie.

Understanding the mechanism of prion propagation is crucial for grasping how these diseases develop and progress, highlighting the importance of protein folding and the potential consequences of misfolded proteins in biological systems.