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prions

GUIDED BYWINSON SAM

PROJECT BY RAHUL D

WHAT IS A PRION

NORMAL FUNCTION OF PRION

HOW PRION BECOME INFECTIOUS

AGENT

DIAGNOSIS AND

TREATMENT

PRION DISEASE

Preventionconclusion

PRIONS A CLINICAL CURIOSITYPrions are protiens that are found mostly abundant in the brain.They doesn’t use energy, they don’t grow, they don’t die. They reproduce via pre-existing prions.All the mammals have prion protein gene. Prions have some normal fuctions in our body. They help in the long term memory. also causes the activation of mylien repair in schwann cell. Prion expression in the stem cell neccesary for self renewal of the bone marrow. Antioxidant activity Prevent neuronal dysfunction

PRIONS THE infective agentNormally prions have the α-helical structure when their conformation changes it form β-sheets. This occurs due to mutation in the prion gene or by infection of infective prion from other source.Then its changes it nature , now it is an infective protien particle that are capable in producing diseases called prion diseases.

Stanley B Prusiner in 1982 coined the word Prion which is derived from the word protien and infection.

Prusiner got the Nobel prize in 1997 for his research into prions.

Normal prions are denoted as PrP and infective as PrPSc.This PrPSc can change normal prions to infective ones.

Prion diseasesIN ANIMALS Scrapie Mad cow disease

IN HUMANS Kuru Creutzfeldt jacob disease Familial insomniaGerstmann–Sträussler–Scheinker syndrome

ScrapieFirst diagnosed prion disease. Found in sheep which affect the nervous system of sheep and its is not transmissible to humans. Clinical signs are behavioral changes increased chewing movement ataxia and intense itching.

MAD COW DISEASENeuro degenerative disease which caused by prions in cows and is also known as Bovine spongiform Encephalopathy and it infects the human beings by the consumption of the contaminated meat and also through its body fluids.

They shows agression and

abnormal posture

Prions disease occur in cattle are mainly due to feeding cattle with the meat and bone meal of infected sheeps.

Infected cows will be dead within 6 months.

Clinical signs Incoordinated body

movement Aggression decreased milk production loss of body weight.

KURUkuru is an incurable degenerative disorder which found in the tribal region of Papua New Guinea is a type of transmissible spongiform encephalopathy caused by the prions. Word kuru derives from the word kuria means to shake and also it is known as laughing sickness.It orginated around 1900, and main reason for its spread is the practice of cannibalism

Cannabalism

Symptoms

Headache, joint pain(first days)

After 6-12 weeks Shaking of body unsttopable laughing

After 12 months Difficulty in walking and speaking

Death within the 2 years.

Nobel prize 1976 to carlton Gadjesek for research in kuru and reason for its transmission.

CRUETZFELDT JACOB DISEASE

CJD is the most dangerous Prion disease with more death rates than the others. CJD is also an incurable neuro degenerative disorder. CJD mainly affect the cerebral cortex. There are four different types of CJD. SPORADIC CJD IATROGENIC CJD GENETIC CJD VARIENT CJD

Sporadic CJDSporadic CJD accounts for 85% of CJD cases, yet remains very rare. It is estimated that one death in every million is caused by sporadic CJD. What triggers sporadic CJD is unknown, but it normally affects people over 40 years of age.

Iatrogenic CJDThis type of CJD is the result of the infection being spread from someone with CJD through medical or surgical treatment.

Familial or genetic CJDThis is a very rare form a CJD caused by an inherited mutation of the gene that produces normal proteins. The altered gene seems to produce prions that then cause CJD. Variant CJD vCJD was identified in 1996. There is clear evidence that variant CJD is caused by the same strain of infection that causes what is known as Mad cow disease . After studies it has been found that it transmitted through the infected meat.

It is a very rare, usually familial, fatal neurodegenerative disease that affects patients from 20 to 60 years in age.

A change incodon 102 from proline to leucine on chromosome 20,

Therefore, it appears this genetic change is usually required for the development of the disease.

Symptoms progressive ataxia dementia.

Gerstmann Sträussler Scheinker syndrome

FATAL FAMILIAL INSOMNIAFFI is an extremely rare autosomal dominant inherited prion disease of the brain. Caused by mutation to the protein PrPC. Progressively worsening insomnia which led Hallucination Delirium Dementia

FFI patients will survive 18 months only. The mutated PrPC has been found in just 29 families worldwide, affecting about 78 people in total. If only one parent have the affected gene the possibility of transfer is about 45%.

DIAGNOSISMagnetic Resonance Imaging (MRI)reveals the characteristics patterns of brain degeneration that help diagnose PrPSc

Electroencephalogram (EEG)record the brain’s electrical pattern which can be particularly valuable because it shows specific type of abnormality in prion proteins

A brain biopsy done to look for spongiform change, which would be diagnostic of sporadic CJD and A brain biopsy is a neurosurgical procedure in which a brain surgeon removes a small amount of brain tissue to be examined for presence of prions.

Cerebro spinal fluid exam In all cases of CJD , an examination of cerebrospinal fluid should be performed. Lumbar puncture, the presence of a particular protein called 14-3-3 in the cerebrospinal fluid is very helpful in the diagnosis of sCJD. The increased level of protein is caused by the rapid loss of brain cells.

BLOOD TEST

TREATMENTCurrently no drug is available for the curing of the prion disease. And some experimental drugs used were Tetracycline compounds, Quinacrine, Pentosan polysulphate, Flupritine.Some future drugs and methods still under studying are PRN-100 an antibodyAnd treatment with RNA interference.

PREVENTION Since the link between mad cow disease and CJD of human was confirmed so° A ban on feeding farm animals on meat and bone meal.° The removal and destruction of all part of an animal carcass infected with BSE.

Prevention of transmission of prion disease through blood transfusion because blood is a good carrier for the prions. So person infectedwith prions should not let to give blood.

Prion disease can also affect by organ transplant so prevent the transplantation of the infected person.

It has proven that infected prion is not affected by normal sterilizing procedure so instruments used for treatment of infected person should not be used again.

There is a chance of transmission with human growth hormone so synthetically produced growth hormones should be used.

CONCLUSIONPrion protien is an amazing protien aswell as a devastating disease causing agent. Prion diseases have no treatment yet. Prevention is the only way to avoid prion disease. CJD is the main disease caused from prions and future studies for the treatment of these disease will lead to curing of several other neuro degenerative disorders.

REFERENCE• Prusiner SB. Shattuck lecture: neurodegenerative diseases

and prions. N Engl J Med 2001;344(20):1516–26.• Liberski PP, Brown P. Kuru: fifty years later. Neurol

Neurochir Pol 2007;41(6):548–56.• Sejvar JJ, Schonberger LB, Belay ED. Transmissible

spongiform encephalopathy. J Am Vet Med Assoc 2008; 233(11):1705–12.

• Aguzzi A, Sigurdson C, Heikenwaelder M. Molecular mechanisms of prion path Ogenesis. Annu Rev Pathol 2008; 3: 11–40.

• Aguzzi A, Heikenwalder M, Polymenidou M. Insights into prion strains and neuro toxicity. Nat Rev Mol Cell Biol 2007; 8 (7):552–61.

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