Prions, Neurons and Glial Cells

Prions are infectious agents primarily composed of protein. Unlike viruses, bacteria, fungi, and other pathogens, prions do not contain nucleic acids (like DNA or RNA). Here's what you should know about them:

1. Nature of Prions: Prions are misfolded versions of a normal protein found in the brain, called the prion protein (PrP). When the misfolded prion protein comes into contact with the normal version of the protein, it induces that normal protein to also misfold. This sets off a chain reaction where more and more proteins misfold and aggregate.

2. Diseases Caused: Prions are responsible for a group of rare, progressive neurodegenerative disorders known as transmissible spongiform encephalopathies (TSEs). These diseases affect both humans and animals. Examples include:

   • In Humans: Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Fatal Familial Insomnia (FFI), and Kuru.
   • In Animals: Scrapie (in sheep and goats), Bovine Spongiform Encephalopathy (BSE or "mad cow disease" in cattle), and Chronic Wasting Disease (CWD in deer and elk).

3. Transmission: While the primary method of transmission is through ingestion of infected tissue, some prion diseases, like CJD, can sporadically appear without known cause or can be inherited. Prions are resistant to many usual methods of disinfection and can remain infectious in the environment for years.

4. Disease Mechanism: Prion diseases lead to brain damage as the misfolded proteins accumulate. This causes the brain tissue to take on a sponge-like appearance under the microscope, hence the term "spongiform" in TSEs.

5. Detection & Treatment: There are no treatments that can cure or control prion diseases currently. Diagnosis can be challenging and often requires a combination of clinical assessment, brain imaging, cerebrospinal fluid analysis, and sometimes brain biopsy. Some tests can support a diagnosis, but definitive confirmation usually requires examination of brain tissue, often after death.

6. Notable Crisis: One of the most widely recognized prion disease outbreaks occurred in the UK in the late 20th century when BSE (mad cow disease) spread among cattle and subsequently led to several hundred cases of the human variant, vCJD, after people consumed infected beef.

Prion research continues to be a crucial area of study, not only because of the direct diseases they cause but also because they challenge traditional concepts of infectivity and might offer insights into other protein-misfolding disorders like Alzheimer's and Parkinson's disease.

How Prions infect Neurons and Glial cells

Prions propagate and spread by converting the normally folded prion protein (PrP^C) into the abnormal, misfolded isoform (PrP^Sc). Here's a generalized step-by-step process of how prions infect neurons and glial cells:

1. Prion Entry: The initial encounter with prions might occur through ingestion (as in the case of mad cow disease) or other routes. Once inside the host, prions can reach the central nervous system (CNS) and come into contact with neurons and glial cells. The exact mechanisms by which prions spread within the organism and gain access to the CNS are not entirely understood but are believed to involve the lymphatic system and the bloodstream.

2. Protein Interaction: The misfolded prion protein (PrP^Sc) interacts with the normally folded cellular prion protein (PrP^C) present on the surface of cells, including neurons and glial cells.

3. Conformational Change: The abnormal prion protein induces the normally folded PrP^C to adopt the misfolded conformation characteristic of PrP^Sc. This is a templated conversion where the misfolded prion essentially "recruits" the normal protein and causes it to misfold as well.

4. Aggregation: As more and more PrP^C proteins are converted into the PrP^Sc form, they begin to aggregate, forming clumps or plaques. These aggregates can be toxic to cells, disrupting cellular functions and leading to cell death.

5. Cell-to-Cell Spread: Once inside a cell, prions can exploit cellular machinery to spread. This might involve endocytic pathways (how cells uptake substances) and exosomes (small vesicles cells release into their surroundings). These processes can facilitate the spread of prions to neighboring cells.

6. Glial Cell Activation: As prions propagate and neuronal damage ensues, glial cells like astrocytes and microglia become activated. Microglia, being the immune cells of the brain, attempt to "clean up" the prion aggregates, while astrocytes might undergo changes that contribute to the spongiform appearance seen in prion diseases. The inflammatory molecules released by activated glial cells can exacerbate the neurodegenerative process.

7. Neuronal Damage and Death: The combination of direct prion-mediated damage, protein aggregation, and secondary effects from glial cell activation leads to neuronal dysfunction and eventually cell death. The extensive neuron loss results in the clinical symptoms observed in prion diseases.

It's worth noting that while the general mechanism of prion infection and propagation is well-established, many specifics, especially regarding cellular entry, cell-to-cell spread, and the exact roles of different cell types, are still subjects of active research.

Glial Cells: function, purpos, location and damage.

Please note: The content on this blog is for informational purposes only and is not intended to provide medical diagnoses or treatment. The information shared is based on frequently asked questions and is sourced from reputable scientific studies. 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742