Newly Discovered Prion Protein Could Cause Fatal Neurodegenerative Disease

Human prion protein structure. molekuul.be/Shutterstock

Prions are mind-blowingly bizarre. These infectious particles arise when normal proteins in the body fold into the wrong shape, triggering a devastating cascade whereby these miscreant proteins cajole their neighbors into adopting the same conformation. And when these build up, it’s bad news for the brain: large amounts of tissue die, resulting in the characteristic spongy appearance seen in patients with prion, or spongiform, diseases like BSE and CJD.

Things may have been quiet in the world of prions for a while, certainly in comparison to the British outbreak of mad cow disease in the 80s, but we have definitely not heard the last of them. Scientists think they have just discovered a new one, marking the first to be identified in humans for half a century. And it could be the cause of a rare, fatal disease called multiple system atrophy (MSA).

As this is currently incurable, researchers are hopeful that the discovery could lead to the development of novel treatments. And of equal importance are the implications of this research for those who work with tissue from MSA patients. Prions are infectious and highly resistant to standard sterilization techniques: no single method seems to be 100% effective at destroying them.

“You can’t kill a protein,” senior study author Kurt Giles from the University of California, San Diego, said in a statement. “And it can stick tightly to stainless steel, even when the surgical instrument is cleaned.” If confirmed, the discovery may therefore necessitate tighter protocols on the handling and treatment of specimens and equipment.

But before we start panicking, back to the discovery: MSA is a progressive disease of the nervous system that often shares the hallmarks of Parkinson’s disease during the early stages, like movement and balance problems. Interestingly, both diseases are characterized by accumulations of a protein called alpha-synuclein in the brain, and some inherited forms have been linked to mutations in the gene that produces this protein. So what if these genetic variations make alpha-synuclein more inclined to misfold, forming prions?

To explore this idea, scientists took brain samples from 14 MSA patients and injected them into mice that were engineered to have models of Parkinson’s disease, possessing a mutated alpha-synuclein gene. Within around four months, all of the mice developed neurodegeneration and displayed accumulation of alpha-synuclein in brain cells. Another group of engineered mice, injected instead with brain tissue from Parkinson’s patients, did not experience brain deterioration.

According to the study, published in PNAS, the findings indicate that the neurodegeneration had been “transmitted” to the mice by the MSA tissue, characteristic of prion diseases. For example, back in the 80s sixty people died from CJD after becoming infected through contaminated surgical instruments. But at this stage, we don’t know whether MSA proteins are transmissible in this manner.

It’s also important to note that, while the paper has labeled alpha-synuclein a prion, it still does not meet all of the criteria for this classification. For example, as prion expert Dr Valerie Sim points out to Live Science, normal mice did not develop neurodegeneration following exposure to brain tissue from MSA patients, only those with mutated alpha-synuclein. Prions should, however, be able to transmit disease in normal animals. 

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