By: N. Shreya Mohan (MSIWM042)
Prions are a misfolded pathogenic form of proteins that have the ability to transfer its misfolded form to the normal shape of the same protein thereby, folding abnormally. The word “prions” was coined in 1982 by Stanley B. Prusiner and it is a derivative name from “proteinaceous infectious particle”. They are responsible for transmitting several lethal neurodegenerative diseases, particularly in human and few other animals. It is believed that the abnormal 3D configuration of the misfolded protein contains infectious properties resulting in turning the surrounding normal proteins into abnormal ones. These infectious agents are very different from other known infectious agent such as virus, bacteria, fungi as, all of them contain a genetic material (either DNA or RNA).
Prions are made up of proteins called as PrP that is generally found throughout the body of healthy humans and animals. But, PrP found in of the infectious prion has a different structure and is very resistant to proteases. Proteases are those enzymes that usually breakdown the proteins in the body. The healthy PrP is known as PrPc while the infectious one is known as PrPSC meaning ‘scrapie’, a disease of prion occurring in sheep. The structure of PrPc is well defined while the structure of PrPSC is poorly defined.
There were two hypotheses explaining the replication of prions. First one was a heterodimer model in which an assumption was made that a single PrPSC molecule binds to PrPc and further catalyzes its conversion to PrPSC. These PrPSC can go and further convert PrPc. But it was difficult to explain the spontaneity of the two molecules, hence it was disproved. Second model assumes that PrPSC exists as fibrils and its ends bind to the PrPc and further convert it into PrPSC. But an exponential growth was observed along with quantity of infectious particles thereby, explaining a breakage in the fibril.
THEIR ROLE IN NEUROGENERATIVE DISEASE–
Prions cause neurogenerative disease by aggregating from outside inside the nervous system. This forms plaque known as amyloids that completely changes the tissue structures. This is visualized by “holes” in the tissue resulting in a spongy-like structure in the neurons. The incubation period of prion-related disease is (5-20 years), but once symptoms appear, they progress very quickly. The result might be brain damage or death. The structure of infectious prions usually is similar to every species and hence there is a little chance that it will get transmitted. However, the human prion disease Creutzfeldt- Jakob is said to be the prion that usually infects cattle, knowans as mad cow disease which severely infects the cattle and is transmitted through contaminated meat. Also, these proteins have been implicated in the ontogeny of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Hunington disease, and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).
All prion-related diseases do not have a cure and are fatal. The clinical trials for the same have not produced successful results yet because of the rarity of disease. Although, some experiments built genetically engineered cattle and mice which lacked the gene which is necessary prion production, therefore, building research on the same.
Symptoms of prion diseases are:
- Rapidly developing dementia
- Muscle stiffness
- Difficulty speaking
life sciences fundamentals and practice I – Pranav Kumar and Usha Mina.
lehninger principle of biochemistry