Major prion protein

Location of PRNP gene in chromosome 20

The major prion protein (PrP) is a protein that in humans is encoded by the PRNP gene. This protein is most prominently known for its role in the pathogenesis of prion diseases, which are a group of progressive neurodegenerative disorders affecting both humans and animals. These diseases are characterized by the accumulation of an abnormal isoform of the prion protein, known as PrP^Sc, which is infectious and can induce the misfolding of normal cellular prion protein (PrP^C) into the disease-associated form.

Structure

The major prion protein is a glycoprotein predominantly expressed in the central nervous system, but it is also found in other tissues. It is anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. The normal cellular form, PrP^C, is rich in alpha-helices, whereas the disease-associated form, PrP^Sc, has a higher beta-sheet content, which contributes to its aggregation and resistance to proteolytic degradation.

Function

The precise physiological function of PrP^C is not fully understood, but it is believed to play a role in cell signaling, copper metabolism, and protection against oxidative stress. It may also be involved in the maintenance of myelin and the regulation of synaptic function.

Pathogenesis

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), occur when PrP^C is converted into PrP^Sc. This conversion can occur sporadically, be inherited due to mutations in the PRNP gene, or be acquired through infection. The accumulation of PrP^Sc leads to the formation of amyloid plaques, neuronal loss, and spongiform changes in the brain tissue.

Genetic Aspects

The PRNP gene is located on the short arm of chromosome 20 in humans. Mutations in this gene are associated with inherited prion diseases such as Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. Polymorphisms in the PRNP gene, such as the methionine/valine polymorphism at codon 129, influence susceptibility to prion diseases.

Related Pages

• Prion
• Creutzfeldt-Jakob disease
• Gerstmann-Sträussler-Scheinker syndrome
• Fatal familial insomnia
• Transmissible spongiform encephalopathy