Question

What are prions, and how do they cause disease? (pages \(138-39\) )

Short answer

Prions are misfolded proteins that transmit their abnormal shape onto normal proteins, causing several fatal neurodegenerative diseases like Mad Cow Disease and Creutzfeldt-Jakob Disease. Prion diseases, also known as transmissible spongiform encephalopathies (TSE), occur due to the accumulation of misfolded prion proteins in the brain. When misfolded prions contact normal PrP^C proteins, they induce conformational changes leading to a chain reaction of misfolding and the accumulation of toxic aggregates in the brain. This interferes with neuron function, causing cell death and severe neurological dysfunction, eventually leading to death. Prevention mainly involves avoiding contaminated animal products and strict guidelines in medical environments. There are currently no effective treatments, but research is ongoing to find new methods of diagnosis, prevention, and treatment.

Step-by-step solution

1. Introduction to prions

Prions are misfolded proteins that can transmit their misfolded shape onto normal proteins. They are abnormal, infectious agents mainly composed of proteins. They are known to cause several fatal neurodegenerative diseases in animals and humans, such as Mad Cow Disease and Creutzfeldt-Jakob Disease.

2. Prion structure

Prions consist mainly of the PrP protein, which is found in the cell membrane of neurons. The normal PrP protein, designated as PrP^C, has an alpha-helix-rich structure. The misfolded version, designated as PrP^Sc, has a higher proportion of beta-sheets in its structure. This structural change results in the protein adopting a different conformation, leading to its infectious properties.

3. Prion diseases and their transmission

Prion diseases are a group of neurodegenerative diseases caused by the accumulation of misfolded prion proteins in the brain. These diseases are also known as transmissible spongiform encephalopathies (TSE) due to the characteristic spongy appearance of the affected brain tissue. Prion diseases can be transmitted through ingestion, inhalation, or direct contact with infected tissues, but they can also arise spontaneously or be inherited.

4. Mechanism of prion-induced disease

When misfolded prions come into contact with normal PrP^C proteins, they can induce conformational changes, converting the normal proteins into the misfolded, infectious form. This results in a chain reaction where more and more proteins become misfolded, eventually leading to the accumulation of toxic, insoluble aggregates in the brain. These aggregates interfere with the normal functioning of neurons, leading to cell death and the characteristic spongy appearance of the brain. As the disease progresses, it causes severe neurological dysfunction and ultimately leads to death.

5. Preventing and treating prion diseases

Preventing prion diseases mainly involves avoiding the consumption of contaminated animal products and adhering to strict guidelines in medical and research environments to prevent cross-contamination. Unfortunately, there are currently no effective treatments for prion diseases. Research is ongoing to find new ways to diagnose, prevent, and treat these devastating conditions. Several potential therapies are under investigation, including molecules that block prion replication or promote the clearance of misfolded proteins. However, finding a successful treatment has proven to be very challenging due to the unique properties of prions.