PrPC

Definition

PrPC, or cellular prion protein, is a normal, naturally occurring protein found in the body, particularly in the central nervous system. It is the non-pathogenic, or non-disease-causing, form of the prion protein that is implicated in a group of rare, fatal neurodegenerative disorders known as transmissible spongiform encephalopathies (TSEs) or prion diseases.

5 Must Know Facts For Your Next Test

1. PrPC is found primarily on the surface of neurons and other cells in the body, anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor.
2. The normal function of PrPC is not fully understood, but it is believed to play a role in copper homeostasis, signal transduction, and neuroprotection.
3. In prion diseases, the misfolded form of the prion protein, known as PrPSc, induces the conversion of normal PrPC into the pathogenic PrPSc form, leading to a self-propagating cycle of protein misfolding and aggregation.
4. The conformational change from PrPC to PrPSc is the key event in the pathogenesis of prion diseases, as the misfolded prions can then spread to other cells and tissues, causing progressive neurodegeneration.
5. Prion diseases are considered to be 'transmissible' because the misfolded prion proteins can be transmitted between individuals, either through direct contact, contaminated medical instruments, or consumption of infected animal products.

Review Questions

• Explain the role of PrPC in the development of transmissible spongiform encephalopathies (TSEs) or prion diseases.
  • The normal, cellular form of the prion protein, PrPC, is the precursor to the pathogenic, misfolded form known as PrPSc. In prion diseases, the conversion of PrPC to PrPSc is the key event that initiates a self-propagating cycle of protein misfolding and aggregation. The misfolded PrPSc proteins can then spread to other cells and tissues, causing the progressive neurodegeneration and sponge-like changes in the brain that are characteristic of TSEs or prion diseases.
• Describe the proposed functions of PrPC and how its normal role may be disrupted in the context of prion diseases.
  • PrPC is believed to play a role in copper homeostasis, signal transduction, and neuroprotection. However, when PrPC undergoes a conformational change and becomes the misfolded PrPSc form, it can no longer perform these normal functions. The accumulation of PrPSc and the subsequent conversion of more PrPC into the pathogenic form leads to the disruption of cellular processes and ultimately, neurodegeneration. Understanding the normal functions of PrPC and how they are impacted by the conversion to PrPSc is crucial for understanding the pathogenesis of prion diseases.
• Analyze the key differences between PrPC and PrPSc, and explain how these differences contribute to the transmissible nature of prion diseases.
  • The key difference between PrPC and PrPSc is their three-dimensional structure and conformation. PrPC is the normal, non-pathogenic form of the prion protein, while PrPSc is the misfolded, pathogenic form. This conformational change in PrPSc allows it to induce the conversion of normal PrPC into more PrPSc, leading to a self-propagating cycle of protein misfolding and aggregation. The transmissible nature of prion diseases is due to the ability of PrPSc to be passed between individuals, either through direct contact, contaminated medical instruments, or the consumption of infected animal products. The misfolded PrPSc proteins can then spread to other cells and tissues, causing the progressive neurodegeneration characteristic of these diseases.

Related terms

Prion:

An infectious agent composed primarily of a misfolded protein, capable of inducing the misfolding of normal versions of the same protein.

Transmissible Spongiform Encephalopathy (TSE): A group of rare, fatal neurodegenerative disorders caused by the accumulation of misfolded prion proteins in the brain, leading to sponge-like changes and neuronal death.

Conformational Change: The process by which a protein molecule assumes a different three-dimensional shape, often resulting in changes to its function or behavior.