2. The word prion is derived from the word infection and protein .
Prion diseases or transmissible spongiform encephalopathies
(TSEs) are a family of rare progressive neurodegenerative
disorders ( loss of structure or function of neurons, including
death of neurons. ) that affect both humans and animals.
known as "mad cow disease" in cattle and “Creutzfeldt -Jakob
disease” (CJD) in humans.
3. in the year 1986 farmers recognized that something
was happening to their cattle.
In farming, it is convenient and healthy for cattle to
be fed soybean meal as a part of their diet.
In England, soybeans don’t grow well, so British
farmers fed their cattle an animal byproduct which
contained the mixed meat and bones of cattle and
sheep.
This practice caused the infected brains, nervous
systems, and blood of infected cattle to be fed to
other cows, thus filling them with an accumulation of
infected meat. Obviously, more and more cows
became infected and more and more cattle began
to die.
4. also
the massive use of
hormones, pesticides and other harmful
substances which destroy the animal's
immune system. When these diseased
animals are eaten by people, then the
people get sick and die.
5. Prions propagate by transmitting a misfolded protein state.
When a prion enters a healthy organism, it induces
existing, properly folded proteins -which is found most
abundantly in the brain- to convert into the disease-
associated, prion form.
Alteration in the conformation of the protein where normal
α-helix structure is converted to β-sheet structure.
the prion acts as a template to guide the misfolding of
more protein into prion form.
These newly formed prions can then go on to convert
more proteins themselves; this triggers a chain reaction
that produces large amounts of the prion form.
Aggregations of these abnormal isoforms form highly
structured amyloid fibers, which accumulate to form
plaques.
6. All known mammalian prion diseases are caused by the
so-called prion protein, PrP.
The endogenous, properly folded, form is denoted PrPC
(for Common or Cellular) while the disease-linked,
misfolded form is denoted PrPSc (for Scrapie )
7. Three-dimensional structure of PrP C (left) and proposed 3D structure of
PrP Sc (right). Alpha helices are indicated in green while beta sheets
are indicated in blue. PrP C is composed primarily of alpha helices
while PrP Sc is composed primarily of Beta pleated sheets.
8. Left: normal prion protein (coloured green) in non-
infected mouse cell cultures.
Right: misfolded prion form (coloured green) in infected
cell which accumulate primarily in vesicles within the cell.
Cell nuclei are edepicted in blue.
9. This
. altered structure is extremely
stable, insoluble and accumulates in
infected tissue, causing tissue
damage and cell death
This structural stability means that
prions are resistant to denaturation
by chemical and physical
agents, making disposal and
containment of these particles
difficult.
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15. It has an incubation period of months to years during
which there are no symptoms, even though the
pathway of converting the normal brain PrP protein into
the toxic, disease-related PrPSc form has started. At
present, there is virtually no way to detect PrPSc reliably
except by examining postmortem brain tissue where
the brain is spongy in form due to death of neurons .
16. Symptoms in Cattle
Difficulty in standing ,difficulty to walk , loss of
coordination and weight loss despite well
feeding accompanied by reduction in milk
production.
One may even observe slight change in
behavior and attitude of the animal that is
affected by mad cow disease.
17. Behavioural Symptoms
Often mood disturbance e.g. aggression
or loss of interest and personality changes
persist into the illness.
Anxiety and depression are fairly common
features. There may also be a lack of
social judgment and disinhibition.
People may prefer to keep to familiar
routines, changes in the regular daily
pattern of events, or new faces may
cause distress and anxiety.
18. Communication Problems
Speech tends to become slurred (dysarthria) and
quiet and as a result speech may become hard to
understand, making communication difficult.
There is often a reduction in the content of
language, word finding difficulties and there may
be repetition of words or sentences. Eventually
the person can become mute.
As the illness progresses the ability to read and
write are gradually lost. Problems may occur with
understanding written material and with spelling
and signing forms; the person may also have
difficulty following instructions.
19. Memory/Cognitive Deficits
Problems develop with memory and thinking
and there is often a general decline in
intellect.
There may be forgetfulness of day to day
events, often accompanied by disorientation
and poor concentration or attention.
Everyday skills that we take for granted may
be lost. Typically the person affected will
forget the day and date. They may also start
to forget how to carry out everyday skills, for
example making a cup of tea. In the latter
stages of the disease the person may become
increasingly unaware of their immediate
environment and the people around them.
20. Movement Problems
Initially there may be a disturbance in balance
and gait, leading to unsteadiness
(ataxia). Walking will therefore be affected and
so extra care will have to be taken to try to
prevent falls.
Involuntary rhythmic muscle contractions leading
to jerky movements (myoclonus) and difficulties
coordinating hand movements leading to
apparent clumsiness. Shakiness (tremor) and
stiffness (rigidity) are often seen.
As movements become increasingly
uncoordinated the individual will need help with
carrying out their daily activities, for
example, personal hygiene and use of the toilet.
21. Swallowing Problems
With the progression of the disease there may also
be difficulty in swallowing. There are a number of
strategies, which may make swallowing easier and
an assessment by a speech and language therapist
can identify problems and give advice regarding
strategies to help.
As swallowing becomes increasingly difficult in the
later stages of the disease, it may be suggested
that nutrition be supplemented with tube
feeding. This issue will require careful consideration
and is rarely done in prion disease. Relatives need
support in making an informed decision. A speech
and language therapist, Macmillan nurse, dietician
as well as your own GP may be able to offer
advice.
22. Visual/Perceptual Problems
Visual problems include double vision and
difficulty moving eyes to follow objects.
Hallucinations are fairly common. There may be a
failure to understand and correctly interpret visual
stimuli. There may be misidentification of
objects/people, whereby something/someone
may not be recognized accurately.
Some patients may suffer from what is known as
cortical blindness, a condition in which an
individual appears to be blind (although the eyes
themselves are normal), due to damage in the
visual processing and interpretation areas of the
brain.
23. Seizures
Very occasionally a person may suffer
from seizures in the later stages of the
disease.
Medication is available to help control
seizures should they occur.
24. Other symptoms
Personality changes
Psychiatric problems
Depression
Lack of coordination
Unsteady gait
Myoclonus
Unusual sensations
Insomnia
Confusion
Memory problems
Severe mental impairment
Inability to move
Inability to speak
25. It has been hard to develop a test for
prion disease because the body’s immune
system does not fight off prion infection by
making antibodies in the same way it does
against germs like bacteria or viruses.
It has been challenging to develop a test
that can distinguish between the normal
prion protein, which we all have in our
blood, and the abnormal form linked to
the disease which is chemically very similar
26. At present, the best diagnostic tests for
CJD use cerebral spinal fluid or actual
brain tissue as test samples; neither is
easily obtained Moreover, the current
spinal fluid-based tests are not fully
sensitive or specific for CJD
27. .Scientists have developed a prototype test. This
involves taking a small blood sample from a patient as
with any other blood test.
A small sample of blood is mixed with special metal
beads to which the rogue prion proteins stick tightly.
These are then washed to remove the normal prion
protein and other blood components that would
interfere with the test.
Finally, the amount of rogue prion protein attached to
the beads is measured using antibodies we have
developed that bind very tightly to the prion protein.
At present the test does not work in other forms of prion
disease such as sporadic CJD but we are hoping this will
be possible with further work in the future.
28. Prions disease is a fungal infection and is
caused by a protein.
There are ways to control, prevent and
infections from spreading.
No treatment has been confirmed to be
a definite cure for prions disease.
Let`s remember that; Prions cause
neurodegenerative disease by
aggregating extracellularly within the
central nervous system to form plaques
known as amyloid
29. Dr. Wisniewski and his colleagues found 68 chemical
compounds, known as styryl-based compounds, his
team screened these 68 styryl-based compounds for
their ability to inhibit prion infection in a standard cell
culture.
They found two that seemed both effective and
non-toxic, and confirmed their effectiveness by
showing that on average they markedly delayed the
onset of symptoms in prion-injected lab mice.
The styryl-based compounds also reduced the signs
of disease in the mouse
30. .they found similar results the
antidepressant trimipramine and the
anti-scizophrenia drug fluphenazine
Both are chemically related to the anti-
protozoal drug quinacrine, which is
known to slow prion infection in cell
cultures,
Although it fails to protect prion-
infected mice or humans. Their
chemical differences from quinacrine
apparently enable the two drugs to
bind more tightly to toxic prion
aggregates, and-like the styryl-based
compounds-prevent these aggregates
from assembling new copies of
themselves.
"One of the trimipramine-treated mice
stayed healthy throughout the 400-
day"…..
Dr. Wisniewski's laboratory's work to
develop potential prion-disease
vaccines.
