Prion protein

The prion protein (PrP) is a protein that is encoded by the PRNP gene in humans. It is best known for its role in the pathogenesis of prion diseases, which are a group of progressive neurodegenerative disorders. These diseases include Creutzfeldt-Jakob disease, bovine spongiform encephalopathy (BSE, or "mad cow disease"), and scrapie in sheep.

Structure

The prion protein is a glycoprotein that is predominantly expressed in the central nervous system, but it is also found in other tissues. The normal cellular form of the prion protein, denoted as PrP_C, is a cell surface protein that is attached to the membrane by a glycosylphosphatidylinositol (GPI) anchor. The structure of PrP_C includes a flexible N-terminal region and a globular C-terminal domain that contains three α-helices and two short β-strands.

Function

The exact physiological function of the prion protein is not fully understood, but it is believed to play a role in cell signaling, copper metabolism, and protection against oxidative stress. PrP_C may also be involved in the maintenance of myelin and the regulation of sleep.

Pathogenesis

Prion diseases are caused by the conversion of the normal prion protein (PrP_C) into a misfolded, disease-causing form known as PrP_Sc. This misfolded form is characterized by a high β-sheet content and is resistant to proteolytic degradation. PrP_Sc can induce the misfolding of additional PrP_C molecules, leading to a chain reaction that results in the accumulation of PrP_Sc in the brain. This accumulation causes neuronal damage and the characteristic spongiform changes seen in prion diseases.

Transmission

Prion diseases can be transmitted through ingestion of infected tissue, iatrogenic means, or inherited mutations in the PRNP gene. The most famous example of transmission is BSE, which can be transmitted to humans as variant Creutzfeldt-Jakob disease (vCJD) through the consumption of contaminated beef.

Diagnosis and Treatment

Diagnosis of prion diseases is challenging and often involves a combination of clinical assessment, MRI, EEG, and cerebrospinal fluid analysis. Definitive diagnosis is usually made post-mortem through brain biopsy. Currently, there is no cure for prion diseases, and treatment is primarily supportive.

Research

Research into prion proteins is ongoing, with studies focusing on understanding the mechanism of prion propagation, the development of diagnostic tools, and potential therapeutic approaches. Animal models and cell culture systems are commonly used in prion research.

Also see

• Creutzfeldt-Jakob disease
• Bovine spongiform encephalopathy
• Scrapie
• Protein folding
• Neurodegenerative disease