Brain: In recent months, 48 cases of a neurological syndrome of unknown origin have been identified in New Brunswick, Canada. Patients presented diverse symptoms, such as delusions, hallucinations, weight loss, aggressiveness, speech and gait difficulties, as well as symptoms of rapidly progressive neurological degeneration, similar to the disease called Creutzfeldt-Jakob Disease (CJD). This is one of the manifestations of a set of invariably fatal diseases known as Transmissible Spongiform Encephalopathies.
It is known that humans and other mammals such as sheep, deer and cattle can develop these diseases. In the almost absolute majority of cases of the disease, the brain takes on the shape of a sponge, hence the name spongiform encephalopathy. In the 1980s and 1990s a form of these diseases, called the new variant of CJD, was transmitted to humans who consumed meat or meat products contaminated by a disease equivalent to that of cattle. What, in popular terms, led the disease to be generically called “mad cow disease”.
Transmissible spongiform encephalopathies are caused by an infectious protein called a prion, which is very resistant to the sterilization process used for other infectious agents, which always leads to serious concerns. However, sanitary control and international legislation reduced the risk of transmission of these diseases to humans.
Fortunately, investigation of these recent cases in Canada has proved negative for diagnostic tests for prion disease. The hypotheses for the emergence of these cases point to the possibility of chronic exposure to toxins found in mushrooms or in a cyanobacterium.
The last time that exposure to these toxins was discussed in the medical literature dates back to the 1950s, with the appearance of a neurodegenerative disease in natives of Guam Island, in the Pacific. Although the investigation of recently described cases in Canada initially ruled out the diagnosis of CJD, these cases have again brought a spotlight to prion diseases.
The term “prion” was created by the American physician and researcher Stanley Prusiner in 1982 to designate an infectious protein capable of spreading and transmitting diseases. Its composition exclusively of proteins has been proven in laboratories and, in fact, does not depend on genetic material (RNA or DNA), which confronted the scientific definition of an infectious agent. This finding was a major breach of dogma in modern biology, which earned Prusiner the Nobel Prize in Medicine in 1997.
The ability of prions to self-propagate is due to their ability to undergo conversion in their three-dimensional folding. In its natural form, which does not cause disease, the prion protein has a very flexible fold, like a small spiral, but when its folding changes, it becomes more rigid, like a staple, and cannot return to its original shape. .
Once the rigid shape is acquired, the infectious protein begins to convert proteins from the natural flexible to the rigid form at an exponential rate, generating a tangle of proteins that accumulate, damage the cell and can spread, spreading the infection.
The phenomenon of altered protein folding has been explored in other more common neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis (ALS).
This concept can bring advances in the knowledge of the common mechanisms between these diseases, as well as others, such as cancer, which may be associated with poor protein folding. We hope that these findings may point to therapeutic possibilities not yet explored.