Scientists from the New York-based Case Western Reserve University (CWRU) School of Medicine recently conducted a study in the Safar Laboratory to learn more about the replication process of prions, which are misfolded proteins known to cause deadly neurodegenerative illnesses in mammals, including humans. Published in the journal PLOS Pathogens, this research study is the first to provide insights into how prions proliferate in the brain and cause damage to cells. To date, research on human prions has been limited due to the extensive biosafety measures required to conduct these types of studies, and because prions are molecularly complex.
First discovered in the 1980s, prions are biological agents that can live and replicate inside living cells. Bovine spongiform encephalopathy, also known as mad cow disease, brought an initial scientific awareness to how prion diseases are capable of self-replication. Spreading like an infection, prions propagate by transforming healthy proteins into toxic ones that cause the development of tiny holes within the brain. As prions spread throughout the brain, they cause it to lose mass and assume a sponge-like form, which leads to dementia and ultimately mortality.
Understanding the replication process of prions is necessary for scientists to be able to develop treatments for multiple types of illnesses involving neurodegeneration, including Alzheimer’s disease. Although Alzheimer’s disease is one of the most prevalent diseases on the planet, scientists still lack a thorough understanding of how the disease is caused. However, many scientists agree that factors related to proteins in the body are involved with the development and spread of the disease, thus necessitating research in this area.
Led by Jiri Safar, the team of researchers involved in the study at CWRU used a three-step process to gain valuable information about the surface and functional features of prions and how they are involved in replication. The team examined brain-derived prions using extremely bright synchrotron x-ray energy with the capability to alter the chemical structure of the prions. The level of brightness of this form of x-ray beam exceeds that of the level of light reaching the earth from the sun by millions of times.
The second step in the investigative process involved analyzing the chemical changes in the prions following exposure to the intense x-ray beams by using anti-prion antibodies. In addition, the second stage of the research evaluated the prions using mass spectrophotometry testing to learn how different strains of prions differ from one another from site to site on the surface of their structure.
During the final part of the research process, scientists replicated the illuminated prions in a test tube environment. As they continued to expose these prions to the synchrotron beams, they observed the functional changes that took place during the replication process.
Scientists are hopeful that the knowledge gained from this study related to the functional properties of prions will contribute to new targeted treatments that can be used to suppress or block the spread of prions. This research provides an initial investigative understanding of how the prions involved with various types of neurodegenerative diseases differ structurally from one another. This research method may also be valuable for determining what factors might contribute to the level of aggression of neurodegenerative diseases. Additional studies are required to gain further knowledge of how prions grow and impact the various types of cells within the brain.