Prion disease (an infectious protein)

What are prions?

Prions are unusual proteinaceous infectious particles that cause a group of universally fatal neurodegenerative disease called the spongiform encephalopathies by an entirely unique mechanism.
The word ‘prion’ was coined by Stanley B. Prusiner in 1982.
Prion is derived from the word protein and infection.
Prions, like viruses, are not actually active, although both can reproduce by hijacking the functions of living cells.
Prions are small protein-containing infectious particles with no detectable nucleic acids.
They are abnormal proteins with an abnormal folding structure (β‐pleated sheets), that have an equivalent protein with the same primary structure within the host, that folds normally (2 α‐helices).
The function of this protein, whose gene is located on chromosome 20, is unknown.
The misfolded protein molecules form aggregates (“amyloid”) that interfere with cellular function.
The normal protein is called PrPc (for prion protein cellular), and the abnormal protein is called PrPsc (for scrapie, a transmissable infectious spongiform encephalopathy of sheep and goats).
The abnormal proteins transmit their information to the normal proteins, causing them to fold abnormally. The abnormal aggregates lead to tissue damage, which affects primarily the brain, leading to a slowly progressive encephalopathy and death.

Different hypotheses have been suggested for the makeup of proteins.
However, the widely accepted hypothesis is the ‘protein only hypothesis’ first suggested by Griffith (1965) and re-established subsequently by Prusiner.
Prions show following features:
- They do not contain nucleic acids.
- They contain an aggregated of hydrophobic glycoprotein resistant to protease.
- The protein present in humans and other animals is called cellular prion protein. It is similar to glycoprotein in scrapie; also known as scrapie prion protein (molecular wt. is 27,000-30,000 Da) in sequence but differs from it in being sensitive to protease and being present in plasma membrane.

The disease is transmitted either orally or transcutaneously by direct contact through body fluids such as saliva, blood, urine of infected animals
The other possible route is by the blood circulation.

PrPsc (scrapic protein) is generated endogenously or enter inside the body through exogenous sources from infected animals or human. But, how the prions reach the CNS, their target is yet unknown. However, It is convinced that the prions may reach the CNS via splanchnic nerves at the level of the thoracic spinal cord and via parasympathetic fibers connecting with the brain.
PrPsc (Scrapic protein) binds to the normal cellular protein (PrPc) of the host found in most tissues but abundantly in the CNS particularly the neurons.
PrPsc is ingested by neurons and phagocytic cells but continues to remain intact without being degraded.
This may support to vacuolation of the neuron, a key pathological alteration seen in encephalitis caused by prions.
In addition, accumulation of prions in high concentration causes damage is the brain tissue.
These include the formation of amyloid containing plagues and fibrils, a proliferation and hypertrophy of astrocytes, and fusion of neurons and adjacent glial cells.

Prions cause neurodegenerative disease by aggregating extracellularly within the CNS to form plagues also known as amyloid which disrupt the normal tissue structure.
The neurogenerative symptoms can include compulsions, dementia, ataxia and behavioral or personality changes.
In all species, it is characterized by spongy appearance of the cerebral gray matter, very long incubation period, slow course, fatal termination, predilection for involvement of CNS, absence of immune response and genetic predisposition.
Prion cause the following diseases in humans:
- Kuru
- Crutzfelt-Jacob disease
- Variant CJD
- Gerstmann-Straussler-Scheinker (GSS) syndrome
- Fatal familial insomnia
- Sporadic fatal insomnia
Prion cause the following diseases in animals:
- Scrapic
- Bovine sporyiform encephalopathy (BSE) also known as mad cow disease
- Transmissible mink encephalopathy
- Chronic washing disease of deer, mule and elk.

The diagnosis of prion disease is always critical.
It is usually confirmed by the histopathology of the brain tissue showing characteristic biological changes.
No serological tests are available.
Detection of protein 14-3-3 in the CSF by Western blot in a sensitive and specific method in the cases of sporadic CJD and in rCJD.
A specific reduction in uric acid level in the CSF have been shown in VCTD but not in sporadic CJD, thus facilitating in the differential diagnosis of VCJD.

Special care while handling materials from patients with CJD or VCJD.
Special disinfection protocols have been developed by WHO for prevention of these diseases.
Autoclaving at 15lbs for 1hr before handling infectious products
Treatment with 0.1M NaOH and 5% hypochlorite solution before handling infectious products.