The word itself derives from ‘proteinaceous infectious
particle’; meaning that the infectious agent consists
only of protein with no nucleic acid genome. Prions
are the only known example of infectious pathogens
that are devoid of nucleic acid. All other infectious
agents, like bacteria, viruses, fungi possess genomes
composed of either DNA or RNA that direct the
synthesis of their progeny
The infectious agent (Prion) consists primarily of a protein
found in the membranes of normal cells, but in this case
the protein has an altered shape or conformation – PrP(
– called scrapie isoform. Prions reproduce by recruiting
) and stimulating its
disease and generates new infectious material. The
process by which prions stimulate the conversion of PrP(
) is not clear.
radiation and X-rays, which breaks down nucleic acids,
suggesting the absence of nucleic acid
, but is susceptible
infectious even after being exposed to treatments that
destroy nucleic acid.
A major feature that distinguishes prions from viruses is
) is encoded by a chromosomal gene
. The gene
for this protein has been successfully cloned, and studies
using transgenic mice have bolstered the prion
According to Dr. Anders Hedberg, phenomenon much like
prion infection exists in yeast. In the yeast, there is passage
of a particular genetic trait from mother cells to daughter
cells along through the cell cytoplasm, rather than the
nucleus which is the site of genetic information.
The structure of PrP(
) and PrP(
) have been studied by
manufacturing these proteins in
E. coli bacteria that were
altered through recombinant DNA techniques. The
polypeptide chains of PrP(
) are identical in
amino acid composition but differ in their three-
dimensional, folded structures (conformations). PrP(
and has little beta-sheet (flattened strands of amino acids),
) is less rich in alpha-helixes and has much
. This structural transition from alpha-
underlying prion diseases.
Prions have been implicated as a causative factor in a
number of fatal neurodegenerative diseases in humans –
such as Creutzfeldt - Jakob disease (CJD), Kuru, and
Gerstmann-Sträussler-Scheinker (GSS) disease. Prions also
cause disease in a wide variety of other animals, including
Scrapie in sheep and bovine spongiform encephalopathy
(BSE) in cows. These diseases are collectively known as
transmissible spongiform encephalopathies
or sporadic disorders. No other group of illnesses with a
single cause has such a wide spectrum of clinical
manifestations. Prion disease in humans (CJD, GSS, and
including dementia (loss of memory), ataxia (instability
of gait), insomnia, paraplegia (weakness of the
extremities), paraesthesia’s (abnormal sensory
perception), and deviant behaviour.
Aetiopathogenesis of human prion diseases
The cause of CJD was unknown for many years; it occurred
seemingly randomly, at a very low incidence. The
infectious form of CJD is believed to be due to eating
infected cows meat. Inherited cases of CJD and GSS may
result from mutations in the PrP gene which encodes for
stable form of prion protein PrP(
. Mutations cause PrP(
to flip into an abnormal form i.e., PrP(
) that causes the
disease by associating with PrP(
) and converting it to
) in an exponential process.
) often accumulates in
them are ineffective
. They completely clog the infected
all. Ultimately, infected prion-bloated brain cells die and
release prions into the tissue. These prions then enter,
infect, and destroy other brain cells
. This process
cheese. The medical term for the prion diseases is
“spongiform encephalopathies,” meaning brain disease
wherein the sick brains (‘encephalo’ is Greek for brain;
‘pathy’ is Greek for disease) are riddled with holes and have
taken the form of sponges
In the 1950s, an epidemic transmissible disease called
Papua New Guinea. Transmission of the disease
occurred during a ritual funeral process in which the
brain of a dead tribe member was removed from the
skull, cooked, and eaten
Institutes of Health, demonstrated that extracts of
brain prepared from people who had died of CJD or
Kuru could cause a similar disease when inoculated
into the brain of chimpanzees, thus suggesting the
presence of an infectious agent. Similar experiments
in mice also produced identical results.
Scientists now speculate that the prions that started out
in sheep suffering from Scrapie made their way into cows
and then moved more recently into humans
. Cattle are
bones and other waste parts of sheep carcasses
prions because of the epidemic of BSE, more commonly
known as mad cow disease. Hundreds of thousands of
infected animals have been eaten by Europeans and
particularly the British over the past 10 years. Research
work suggests that the infected meat may pose a threat
to human health, but the significance of that threat may
not become apparent for years. The US Department of
Agriculture claims that BSE has not been identified in any
US cattle so far
, hence it is generally considered a British
The exact mechanism by which prions stimulate the
) to PrP(
site of entry to the brain.
Drugs that can effectively eliminate prions from the
It is likely that prions can be a causative factor in a
diseases in which brain cells are destroyed and the
nervous system deteriorates. Alzheimer’s disease and
Parkinson’s disease are two prime candidates.
Aguzzi A, Weissmann C. Spongiform encephalopathies: a
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helices into (beta)-sheets features in the formation of the
scrapie prion proteins.
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et al. A novel
progressive spongiform encephalopathy in cattle.
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In 1927, Cecil A Alport described 3 generations of a family
with combination of progressive hereditary nephritis and
deafness. The eponym Alport syndrome (AS) was coined
. It is a genetically heterogeneous disease
type IV collagen located on X chromosome Xp 29. The a5
subunit is a major component of basement membranes
of glomerulus, cochlea, retina, lens capsule, and cornea.
Rarely, it may be caused due to a defect in the a3 or a4
subunit. The characteristic histo-pathological feature is
progressive degeneration of basement membranes in
eyes, ears, and kidneys. Eye changes comprise of anterior
and/or posterior lenticonus, lenticular opacities, and
recurrent corneal ulcerations. Ear changes result in sensori-
neural deafness. In kidneys, the lack of a3, a4, and a5 chains
of type IV collagen are replaced by a1 and a2 chains.
Basement membrane changes in kidneys pass through
various stages from normal to thinning and progressing
to thickening, splitting, and degeneration manifesting as
asymptomatic urinary abnormalities to chronic renal
18 years old male presented to eye OPD with a history of
progressive diminution of vision for last ten years. He was
unable to achieve satisfactory vision despite repeated
change of glasses for refractive errors. On questioning, he
also told about non-progressive impairment of hearing since
childhood. There was no history of ear discharge, giddiness,
and tinnitus. There was no history of drug intake, headache,
vomiting, cranial nerve palsy, or focal neurological deficit.
His family history revealed that his younger brother had
died of congestive heart failure with renal failure at the
age of 14, and both of his maternal uncles had died of
renal failure. His three sisters are healthy and had normal
ophthalmological and urine examination.
His general physical examination was non-contributory
and he was normotensive. Eye examination revealed visual
acuity of 6/60 in right eye and 6/24 in left eye without any
improvement with pinhole. Intraocular pressure and
indirect ophthalmoscopy was normal. Slit lamp
examination showed normal anterior chamber, distorted
anterior spherical curvature with anterior coning (Fig. 1)
and posterior coning (Fig. 2) of lens with lenticular opacity.
Distant direct ophthalmoscopy revealed positive oil
droplet reflex. Hearing test showed a positive Rinne’s test,