Prions are small infectious protein particles responsible for fatal Neurodegenerative diseases in humans and animals. Different from viruses & viroids and they do not contain nucleic acids. Prion is actually misfolded protein.
All organisms including prokaryotes, eukaryotes & viruses possess nucleic acids. But nucleic acids are absent in some infectious agents and they are called as prions.
In 1982, American Scientist Stanley B. Prusiner isolated and purified such infectious agents. He coined the term 'Prion' by combining first letters of the words proteinaceous and infectious and -on to make analogy to Piron.
In 1997, Prusiner was awarded the Nobel Prize in medicine and physiology.
Characteristics of Prions :
- Chemically prions are glycoproteins.
- Prions do not contain DNA, RNA or capsids.
- Prions consist of only hydrophobic protein of 33 to 35 kilodalton (253 amino acids). which is often called Prp (Protease resistant protein).
- Prions are responsible to cause Neurodegenerative discase in which large vacuoles are produccd in the brain tissue.
- Prions have not been visualised.
- Prions are highly resistant nucleases & UV radiations.
- They are sensitive to chemicals that denature proteins.
- They are also sensitive to heat.
- They cause slow infections. The incubation period ranges from one to several years.
- Prions are very difficult to decompose biologically; they survive in soil many years.
- Prion discases are transmitted directly from one person to another, indirectly by fomites and by the ingestion of contaminated meat.
Types of Prions :
Prions are mainly 2 types
1) PrPc (C=cellular)
2) PrPsc (sc = Scrapie)
PrPc
- PrPc is a Cellular prion protein
- Gene of PRPc is located on chromosome no. 20.
- PrPc protein consists Alpha helix- 43% and Beta sheets- 03%
- PrPC present on surface of cell.
- PrPc Prion proteins involved in communication between neurons, cell death, and controlling sleep patterns.
- Mutation in PrPc gene which leads to conversion of Aspartate into aspargine was observed in diseased individual.
PrPsc
- PrPSc is a Scrapie form of Misfolded protein
- PrPSc prions are Protease resistant
- PrPSc consists Alpha helix 30% and Beta sheets- 43%.
- The second type of prion protein, known as PrPSc, is the disease-causing form. Organisms with it develop spongiform disease.
- These misfolded proteins were observed to be build up in thalamus region.
The prion diseases are often called transmissible spongiform encephalopathies because of the appearance of holes in the brain tissue.
Replication of Prion :
Scientists are still working out the details, but evidence supports the idea that when PrPc comes into contact with PRPsc it is converted to PrPsc.The result is a chain reaction that multiplies copy after copy of the infectious prion. Because of their abnormal shape, PrPsc- proteins tend to stick to each other. Over time, the PrP-SC molecules stack up to form long chains called "amyloid fibers".
Prion Disease and Symptoms
The common symptoms of Transmissible Spongiform Encephalopathies (TSE's) are :
- loss of muscle co-ordination which leads to difficulty in walking
- Dementia which is characterized by the loss of memory, diminished intellect & poor judgment
- Progressive insomnia (inability to sleep)
- Progressive paralysis and death.
One of the most common disease known to be caused by prions is the "Scrapie" of Sheep & Goat. It causes the animal to scrap or scratch itself against obstacles such as rocks or trees due to itching sensation.
High level of kuru appear among the Fore people of Popua New Guniea. Kuru is a one type of Prion disease.
