Prions are the sub-viral agents, which function as a proteinaceous infectious particle without a genomic RNA or DNA. These are the pathogens that not only cause severe fatal and transmissible neurodegenerative diseases in humans and also in the animals. Prions are composed solely of PrP proteins.
A term prion was coined by a scientist named Stanley Prusiner . Prion diseases are very infrequent, but always fatal. The symptoms of prion infection can progress rapidly that requires proper medical care to control the further spread of the infection.
Meaning of Prion
Prions define as the misfolded proteins or the infectious particles, which can transform the normal variants into the infectious type by some unknown mechanism. They are characterized by transmissible neurodegenerative diseases that are fatal to humans and animals, by causing pores in the spongy tissue of the brain and giving it a spongy architecture.
Prions aggregate into the abnormal protein type that refers as amyloid fibres. These abnormal protein fibres accumulate in the infected tissue and cause deterioration of the cell tissue and finally into cell death. The prion aggregates are structurally stable and resistant towards the action of chemical and physical agents.
Prions exist in two morphologically and functionally distinct states:
It is the cellular and common endogenous prion protein that is non-infectious and found primarily in the central nervous system and various bodily tissues. PrPC is well defined in structure. It mainly possesses alpha-helical structure and consists of 209 amino acids (in humans), one disulfide bond. The normal state of prion has a molecular mass of 35–36 kDa.
PrPC protein is non-sedimentable. The normal form of prion is sensitive to the cellular enzymes. Proteinase K can readily digest the PrPC protein. PrP protein plays a significant function in cell adhesion and intracellular signalling in vivo. Thus, PrPC protein or the cellular protein facilitates cell-cell communication in the brain.
When the PrPC undergoes structural changes, it gets misfolded into a PrPSC state. It possesses a high proportion of β-sheet structure instead of a normal α-helix structure. PrPSC is the infectious state that results into the formation of “Amyloid plaques” which then leads to neurodegeneration.
It is certainly polydispersive in structure. Here, SC refers to ‘scrapie‘ (the prototypic prion disease). The mechanism for the change of normal prion to the misfolded or abnormal state is not known, but the abnormal state transmits its infectious properties by collapsing with the nearby protein molecules into the same state.
The misfolded structure of PrP shows resistance towards the enzymatic activity of proteases that can degrade proteins. PrPSC protein-fiber ends function as a template, where the free protein molecules may attach, to grow the fibre. The amino acid sequence of the infectious PrPSC incorporates into the normal variants of protein in the growing fiber.
Replication Cycle of Prions
Heterodimer model: It explains how prions replicate via protein only. This hypothesis predicted that an infectious PrPSC molecule when interacts with a normal PrPC molecule, it mediates its transformation into PrPSC. Then the two PrPSC molecules segregate to transform more PrPC into the abnormal PrPSC molecules.
Fibril model of prion propagation: An alternative model explains that PrPSC possesses fibrillar structure whose ends bind with the normal endogenous PrPC molecules and transform it into PrPSC.
After the conversion and propagation of prions, the aggregated infectious particles form amyloid fibres, which accumulate in the infected tissue as amyloid plaques. Therefore, it is believed that the abnormal form of prion PrPSC originates spontaneously and transmitted through various ways like food ingestion, mechanical transmission etc. where it directly interacts with an endogenous PrPC protein and enables its structural distortion.
The mechanism behind the conformational change is still not clear, but it is believed that the cellular protein (Protein X) is associated with the transformation of PrPC to PrPSC. The replication mechanism of prions create implications in drug designing, because of its long incubation period. An effective drug can simply slow down the exponential growth of prions by binding to the fibril ends and blocks them from growing any further.
Prions are the infectious particles, which primarily cause neurodegenerative disorders in both humans and animals.
CJD: It stands for Creutzfeldt Jakob disease. It is a kind of degenerative neurological disorder occurring in human, and is invariably fatal. It leads to dementia and ultimately death. Sometimes, it also refers as human form of “Mad Cow Disease”.
vCJD: It stands for variant Creutzfeldt Jakob disease. It is also a neurodegenerative disease that relatively effects the adults and remains for the longer duration of illness.
Fatal Familial Insomnia: It is a heritable autosomal dominant disease of the nervous system that causing difficulty in sleeping.
Kuru. This disease is seen in New Guinea that mostly affected the women and children. In early stage, it causes involuntary tremors and during later stage it leads to dementia, resulting into death.
Bovine Spongiform Encephalopathy: It commonly known as “Mad cow disease” that mainly affects the cow’s nervous system. It is a kind of neurodegenerative disorder that makes the brain spongy, after which the cow act strangely and mad and lose their ability to perform involuntary functions.
Chronic Wasting disease: It has been only found in the members of deer family that causes chronic waste loss leading to death. The first case was seen in mule deer in wildlife research of Northern Colorado, USA.
Scrapie: It is a neurodegenerative disease that primarily affects the nervous system of sheep and goats. It also known as “Rida”.
Feline Spongiform Encephalopathy: It affects the members of the cat family and is invariably fatal.
Risk factors for prion disease include:
- Any member in the family history infected with the prion disease.
- People who have consumed meat infected by prions.
- People infected via contaminated medical equipment.
- Rapidly developing dementia
- Difficulty walking and changes in gait
- Muscle stiffness
- Difficulty in speaking
Prion disease in a person can be diagnosed by various ways, but it should be considered in all people with rapidly progressive dementia.
Sample collection: The sample of brain tissue can be collected during a biopsy or after death. Samples of spinal tap or lumbar puncture can also be taken, followed by performing blood tests.
MRI (magnetic resonance imaging) also helps in the diagnosis of any injury in the nervous system by simply scanning the brain.
Electroencephalogram analyzes brain waves, which requires placing electrodes on the scalp. Neurologic and visual exams can also be found helpful to check any kind of nerve damage and vision loss.
The products must be labelled that contain rendered cattle or sheep. Manufacturers must prevent ruminant products from being mixed with the rendered products. By taking certain precautions, the disease can be prevented.
Proper sanitation should be maintained and if anyone is dealing with any kind of neurological disorder, that person should not donate organs or tissue.