Molecular biologists at Case Western Reserve University (USA) have synthesized the first artificial human prion. This will help develop therapies for prion diseases, since animal models are not suitable for evaluating the effectiveness of therapy. At the moment, such diseases that affect and destroy the brain are incurable. This was announced in a press release on MedicalXpress.
Prions are a special class of infectious agents, which are proteins with an abnormal structure. They are able to catalyze the conversion of normal membrane proteins PrP into the same prions. As a result, a chain reaction starts, during which a large number of abnormal molecules are formed. The latter bind to each other, forming amyloids - growing protein aggregates that accumulate in tissues and cause tissue damage. With Creutzfeldt-Jakob disease (spongiform encephaly), the cortex of the cerebral hemispheres and other parts of the brain is destroyed, which inevitably leads to the death of the patient.
Scientists have already learned how to synthesize prions that infect rodents, but experiments on humanized animals (with implanted human genes) have shown that these proteins are not capable of infecting humans. In the course of the new work, the researchers managed to create a prion pathogenic for humans from the genetically modified PrP protein, the DNA of which was introduced into the Escherichia coli bacterium. Biologists have also found that the GM1 ganglioside protein, which is involved in the regeneration of nerve tissues, promotes the proliferation of prions and the transmission of disease from a sick person to a healthy one.
In addition, it turned out that the rate of prion replication, infectivity and vulnerability of certain brain structures is determined not by the presence of misfolded proteins as such, but by modifications in the structure of the molecule, in particular the C-terminal domain - a fragment located at one of the ends of the junction.
