Prion

INTRODUCTION:
  • The word prion is derived from the word infection and protein .
  • Prions are most resistant organisms to antiseptics & sterilization
  • Prions are Encoded by viral genome
  • Prion diseases or transmissible spongiform encephaloathies (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.
  • Disease associated with prions: Prions are best killed by Sodium hydroxide
  1. Scrapie
  2. Creutzfeldt -Jakob disease 
  3. Kuru (human)
  4. Fatal familial insomnia
  5. Bovine spongiform encephalopathy
  6. Transmissible mink encephalopathy
CAUSES OF PRIONS
  • 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.
  • Acts as a template to guide the misfolding of more protein into prion form.
  • Prion protein diseases is Commonly manifested as dementia
  • 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.
  • 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 )
  • 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.
CLINICAL FEATURES:
  • 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 .
  • Behavioural Symptoms
  1. Often mood disturbance e.g. aggression or loss of interest and personality changes persist into the illness. 
  2. Anxiety and depression
  • Swallowing Problems
  • Communication Problems
  • Memory/Cognitive Deficit
  • Seizures
  • Double vision and difficulty moving eyes to follow objects,cortical blindness Hallucinations are fairly common
  • Movement 
  1. Initially there may be a disturbance in balance and gait, leading to unsteadiness (ataxia). 
  2. Involuntary rhythmic muscle contractions leading to jerky movements (myoclonus) and difficulties coordinating hand movements leading to apparent clumsiness. 
  3. Shakiness (tremor) and stiffness (rigidity) are often seen.
DIAGNOSIS:
  • Now newer immunological and molecular genetic techniques are being used.Conformation dependent immunoassays is extremely sensitive and quantitive and is likely to find wide application in both post and antemortem detection of prions.
  • Brain biopsy
  1. In humans, the diagnosis of CJD can be established by brain biopsy if PrPsc is detected.
  2. The diagnosis can also be made when following features are seen in biopsy (even if PrPsc is not detected).
  3. Spongioform degeneration and astrocytic gliosis
  4. Lack of inflammatory responsePresence of Amyloid plaques
CT
  • May be normal or show cortical atrophy
MRI
  • It is valuable .for distinguishing sCSD from most other conditions.
EEG
  1. Early phase
  2. Normal or scattered theta activity.
  3. Advanced phases
Exam Question
  • Prions associated disease are Scrapie, Kuru,Creutzfeldt jakob disease,Fatal familial insomnia,Bovine spongiform encephalopathy & Transmissible mink encephalopathy Prion is Protein
  • Prions disease are Neurodegenrative desease caused by infectious proteins
  • Prions catalyses abnormal folding of other proteins
  • Secondary structure of prion proteins in prion disease like Creutz feldt-Jakob disease (CJD) is Beta sheets
  • Prions are most resistant organisms to antiseptics
  • Prions is most resistant to sterilization
  • Prion protein diseases is Commonly manifested as dementia
  • Prions are best killed by Sodium hydroxide
  • Prions are Encoded by viral genome
  • Fatal familial insomnia is associated with prion diseases
  • Kuru is a prion disease associated with human

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