Infectious agent made of proteins WHICH
ARE NOT ASSOCIATED WITH A
Infect by folding and unfolding into
The abnormally folded molecule is able to
convert proteins into correctly folded form
This process perpetuates the infection
HUMAN PRION DISEASES
CREUTZFELD-JACOB DISEASE( 1 PER
MILLION PEOPLE PER YEAR)
FATAL FAMILIAL INSOMNIA
All known prions are believed to
infect and propagate by formation of
an AMYLOID fold, in which the
protein polymerizes into a fiber with
a core consisting of tightly packed
BETA SHEETS. Other mechanisms
may exist in yet undiscovered
infectious protein particles.
KURU – NEW GUINEA
Encephalopathy (BSE), also
known as "Mad Cow
BSE disease," has emerged as
one of the most serious
health concerns of the 21st
No one knows for certain
what causes BSE or its
Creutzfeldt Jakob disease
(CJD). However, a majority
of scientists suspect the
culprit may be an aberrant
protein known as a prion
found in the brains and
spinal tissue of infected
Experts also believe
outbreaks of BSE in
European cattle stem from
the once common practice
of feeding these animals
AMYLOID PLAQUES IN
Holes produced by the
Prions - Genetics
The prion is a product of a human gene, termed the PrP gene,
found on chromosome 20.
This gene contains two exons separated by a single intron.
Exon I and Exon II are transcribed and the two RNAs
ligated into a single mRNA. This mRNA contains an open
reading frame (ORF) or protein coding region which is
translated into the PrP protein.
The PrP protein is a precursor of the prion protein. It is
termed PrP 33-35.
The PrP 33-35 undergoes several post-translational
events to become the prion protein (PrP 27-30):
1. Glycosylation - at two sites.
2. Formation of a disulfide bond between two
3. Removal of the N-terminal signal peptide.
4. Removal of the C-terminal hydrophobic
5. Addition of a phosphatidylinositol glycolipid at
6. Removal of the N-terminal first 57 amino
Humans and infections
3. Corneal transplants
A strain of mice that has a
predisposition to prion related
Appears to be a dominant pattern
Genetic predisposition for Scrapie in
Scrapie susceptible sequences have
been located in sheep in New Zealand
FATAL FAMILIAL INSOMNIA;
FFI( OMIM) -
Although the thalamus is affected in diffuse degenerative
processes of the nervous system, a genetically determined
degenerative disease limited to selected thalamic nuclei seems to
have been described first by Lugaresi et al. (1986).
They reported the case of a 53-year-old man who presented with
progressive insomnia and dysautonomia (pyrexia, diaphoresis,
myosis, and sphincter disturbances).
Dreamlike status, dysarthria, tremor, and myoclonus subsequently
developed and led to coma and death after 9 months. Two sisters
of the patient and many relatives over 3 generations had died of a
Pathologic studies of the brains of the patient and 1 of his sisters
showed severe neuronal degeneration, with reactive astrocytosis
limited to the anterior and dorsomedial thalamic nuclei and without
spongiosis or vascular or inflammatory changes.
Mice – Experimental
Mice inoculated with brain homogenates from
subjects with fatal familial insomnia or sporadic
fatal insomnia had lesions of similar types and
distributions in their brains.
In both familial and sporadic fatal insomnia, the
molecular mass of the Prp(Sc) fragment was 19 kD
in these mice.
In contrast, these characteristics were different
in the mice inoculated with homogenate from
patients with typical sporadic or familial
Creutzfeldt-Jakob disease, and the molecular
mass of their PrP(Sc) was 21 kD.