The prion proteins that the body produces “may keep nerves healthy”, BBC News reported. The website says that prions play a vital role in maintaining nerve health, and it is possible that an absence of prions causes diseases of the central nervous system.
While malformed prion proteins have been previously implicated in conditions such as variant Creutzfeldt-Jakob Disease (CJD), this laboratory study in mice may have identified a role for normal prion proteins. Through a number of experiments, the researchers found that removing prions directly from nerve cells led to the degeneration of the cells and an associated reduction in nerve function.
BBC News highlights an important bottom line, saying that it is too early to pick out a particular nerve condition that might correspond to the mouse experiments. Also, the mice in this research were resistant to prion diseases that are equivalent to CJD in humans. This means that it is unclear how these findings apply to the treatment or prevention of human prion diseases. This important science will pave the way for further research into the role of healthy prion proteins in human cell function.
Where did the story come from?
The study was carried out by Dr Juliane Bremer and colleagues from University Hospital Zurich, the University of Würzburg, California Institute of Technology, the Max-Planck Institute for Experimental Medicine in Germany, and RWTH (Rheinisch-Westfälische Technische Hochschule) Aachen University in Germany. Some researchers were funded by individual grants from a number of sources, but there is no apparent external funding specifically for this piece of research.
The BBC has covered this story in a balanced way. It highlights early on in its report that as this was a study in mice, caution should be exercised when extrapolating results from animal research to human health.
What kind of research was this?
The researchers aimed to find out more about the function of normal prion proteins, which are found in the membranes of the body’s cells. They were particularly interested in how they might play a role in maintaining the health of peripheral nerves, the types of nerves that connect arms and legs to the spinal cord and brain (the central nervous system).
Prion proteins can also occur in a malformed variety, which is associated with ‘prion diseases’, such as CJD and its variants. However, this research was only looking at the role of normal prion proteins, known as PrPC, which is still a relatively unexplored subject.
Previous studies have shown that mice that were unable to produce prions (in their healthy form), developed a late-onset disorder of their peripheral nerves (i.e. outside of the brain and spinal cord). The problems that occurred when the mice lacked prions suggests that the proteins may normally play a role in maintaining nerve health.
The researchers say that in humans, PrPC may also have a role in these types of nerve disorders, which they say are highly prevalent human diseases for which the available treatment is often unsatisfactory.
What did the research involve?
Several different experiments were conducted, using mice that were unable to produce PrPC. The development and function of their nerves was assessed through a series of complex laboratory experiments in which researchers examined how the absence of PrPC affected nerve structure. They also looked at how a lack of PrPC affected the way impulses were conducted between the central nervous system and other parts of the body.
In addition to the investigations on the nerve cells, the experiments compared the behaviour of mice that were unable to make PrPC with those that could. For example, they compared each group's response to heat by timing how long it took the mice to lick their paws when standing on a hotplate. The researchers were also able to limit the absence of PrPC to particular cells of the nervous system. This enabled them to investigate exactly which cells used PrPC to maintain nerve health.
Generally, the experiments compared the biology and behaviour of mice that could not produce PrPC with normal, non-genetically modified mice that produced PrPC.
What were the basic results?
At 60 weeks of age, all of the mice lacking PrPC showed signs of damage in their peripheral nerves. This was chronic demyelinating polyneuropathy, a problem where the protective myelin sheath of the nerves was damaged. A series of experiments revealed more detail about this myelin sheath neuropathy, suggesting that it affected the fibres that carry signals both to and from the brain.
The researchers found that when only the nerve cells themselves lacked PrPC, the myelin sheath was still damaged. However, this damage was not present when the inability to make PrPC was restricted to the Schwann cells that surround the nerve.
How did the researchers interpret the results?
The researchers conclude that the “expression of PrPC by neurons is essential for the long-term integrity of peripheral myelin sheaths”, i.e. damage will occur when nerve cells are unable to make the healthy form of the prion protein. They have found that PrPC is vital to the health of peripheral nerves in mice. Without it, pathologies develop.
The researchers emphasise the potential benefit of these findings for people with peripheral neuropathies (nerve diseases that can be caused by diabetes or infections), saying that “clarifying the molecular basis of these phenomena might lead to a better understanding of peripheral neuropathies, particularly those of late onset”. They say this might help to uncover new therapeutic targets for some “common, debilitating disorders”.
This laboratory study will be of interest to neuroscientists and those interested in the science behind neurological disorders. While prions have been linked to diseases such as CJD and its variants, this study was not investigating this disorder. The study found that mice that were unable to produce the normal version of the prion protein (which occurs in healthy cells) developed long-term peripheral nerve damage. This nerve damage was similar to peripheral neuropathies seen in humans. Researchers therefore investigated the role that PrPC (the healthy prion) plays in maintaining the health of peripheral nerves.
This is well-conducted research with a well-described methodology. But as it was performed on animals, caution should be exercised when speculating how relevant these findings are to human disease. However, the researchers say that the normal version of the prion protein PrPC is “well conserved between species”, suggesting that this protein may have similar functions in other animals, too. This remains to be seen in further laboratory research.