Prions

What are transmissible spongiform encephalopathies (TSEs)?

Always-fatal, neurodegenerative brain diseases caused by infectious proteins called prions, characterized by spongiform changes in brain tissue

Why are TSEs described as “transmissible,” “spongiform,” and “encephalopathies”?

Transmissible because they can be experimentally transmitted; spongiform due to microscopic vacuoles in brain tissue; encephalopathies because they are diseases of the brain

What infectious agent causes TSEs?

Prions

Why are prions infectious agents?

They are misfolded versions of normal proteins (PrP) that cause other proteins to misfold

What are the major diseases caused by TSEs?

Scrapie, bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD), variant CJD (vCJD), kuru, and chronic wasting disease (CWD)

What is scrapie and which animals does it affect?

The oldest known TSE; a neurodegenerative disease of sheep and goats characterized by compulsive scraping behavior; not thought to be transmissible to humans.

What is bovine spongiform encephalopathy (BSE) and how did it spread?

A progressive fatal neurological disease of cattle; spread through feeding cattle remains of other animals; known as “mad cow disease.”

How is BSE linked to human disease?

Consumption of BSE-infected cow brain or spinal cord can cause variant Creutzfeldt-Jakob disease (vCJD) in humans.

What is Creutzfeldt-Jakob disease (CJD)?

A rare, fatal human TSE that occurs in sporadic, hereditary, or iatrogenic forms; not spread by casual contact.

What distinguishes variant CJD (vCJD) from classic CJD?

vCJD is linked to consumption of BSE-infected cattle products and emerged in humans in the mid-1990s.

What is kuru and how was it transmitted?

A human TSE found in Papua New Guinea, transmitted through ritual cannibalism; characterized by tremors and long incubation periods.

What is chronic wasting disease (CWD) and which animals are affected?

A TSE affecting mule deer, white-tailed deer, elk, and moose; transmission to humans is unknown.

What is the prion theory?

The “protein-only” hypothesis proposed by Stanley Prusiner stating that infectious agents can be composed solely of protein without nucleic acid.

What is PrPᶜ (PrPC)?

The normal, non-infectious cellular prion protein found on neurons; rich in α-helices, soluble, and protease-sensitive.

What is PrPˢᶜ (PrPSc)?

The infectious, misfolded form of the prion protein; rich in β-sheets, insoluble, protease-resistant, and prone to aggregation.

How does PrPSc propagate in the brain?

By inducing irreversible conformational changes of PrPC into PrPSc, leading to accumulation and aggregation.

Why do prions not trigger an immune response?

Because they are misfolded forms of a host protein and contain no nucleic acid.

What are the major neuropathological features of TSE diseases?

Neuronal death, amyloid plaque formation, accumulation of insoluble protein aggregates, and spongiform (sponge-like) brain tissue.

What are common clinical symptoms of TSE diseases?

Long incubation period, personality changes, psychiatric symptoms, lack of coordination, involuntary movements, dementia, and eventual loss of speech and movement.

How can prion diseases arise in terms of origin?

They can be infectious, hereditary (mutated prnp gene), or sporadic.

What are the most and least efficient routes of prion transmission?

Most efficient: intracerebral; least efficient: oral (intragastric).