Intro to Prions Flashcards
What is a prion?
The abnormal from of a protein which includes pathogenic forms that arise spontaneously or is transmitted and when accumulated in the brain causes prion disease
What is the difference between a normal and abnormal prion?
Alpha helix is health prion
Beta sheet is an abnormal prion
What levels of structure can proteins have?
Primary (amino acid sequences)
Secondary (amino acid sequence linked with hydrogen bonds)
Tertiary (when attractions form between alpha and beta)
Quaternary (a protein consisting of more than one amino acid chain)
What is the history of a prion?
Proteinaceous infectious particle
What are the characteristics of a prion?
Remains infectious after treatment
Rendered inactive by protein ornlipid disrupting agents
Self replicate (no DNA needed for transmission)
What is a prion protein?
PrPc is a membrane glycoproteib birnall expressed in a variety of cells
What is the role of a prion protein?
Stress protection, copper homeostasis and neuronal excitabilty
What are the 2 forms of prion proteins?
PrPC (cellular): endogenous and a-helix
PrPSC (Scrapie): disease linked, and misfolded b-sheet
Why do abnormal prions cause disease?
PrPSC has a strong tendency to self-aggrgate and form fibrils
In which ways do prions become abnormal?
Interaction with an abnormal prion, causing conversion
Spontaneously
Inoculation of PrPSC
What disease group do prions cause, and its characteristics?
Transmissible spongifrom encephalopathies (TSE) Rare Infectious Caused by abnormal prion accumulation Causes neuronal loss, astrocyte prolif and vacuolation of the brain Variable incubation (60d - yrs) Gradual Untreatable and fatal
What are the forms of human prion disease?
Genetic: mutation in prion protein encoder (PRNP)
Sporadic: unknown (most common)
Acquired: transmission by animal or another human
What is generic prion disease?
10-15% 30 different PNRP mutations Autosomal dominant Creutzfeldt-Jacob disease Fatal familial insomnia Gertsmann Steaussler-Scheinker syndrome
What is sporadic prion disease?
Most common (85%) 1 per million cases Diet not cause Caused by spontaneous informational change Can be transmitted iatrogenically
What is acquired prion disease?
Kuru: Papua new Guinea transmitted by cannibalism
Variant CJD: from BSE contaminated meat
Iatrogenic CJD: medical or surgical procedures
Name animal prion diseases?
Bovine spongiform encephalopathy: cattle
Scrapie: sheep
Chronic wasting disease: deer and elk
What is variant CJD?
Incubation of 12 years average
Involvement of the lymphoreticylar system
Transmitted by BSE in cattle via food
What is iatrogenic CJD?
Most cases arose from contaminated human grown treatment in children or a dura mater graft
Blood transfusion, transplantation and electro therapy
PrPSC demonstrated in tonsil, spleen and lymph nodes
What are the clinical manifestatiob of sporadic CJD?
Onset at 60 years
Rapidly progressive dementia less than 1 year
Cerebellar ataxia (disable voluntary muscular movements)
Myoclonus (irregular involvement muscle contraction)
Fatal (90% within 12 months)
What are the clinical manifestation of variant CJD?
Younger (death at 29 years)
60% of patients present with psychiatric symptoms (anxiety, insomnia and withdrawal)
After 4 months clear neurological signs such as gait disturbance, slurred speech and tremors
Involvement movement, cognitive impairment and ataxia after 6 months
Longer around 14 months
CJD histopathology?
Many vacuoles present in brain tissue
Diagnosis of CJD?
Hard (definitive at post-mortem)
MRI (suggestive not definite)
CSF: 14-3-3 analysis (neuronal proteins found in CSF, but could be other disease)
EEG: normal rhythm gradually lost (only sporadic)
Tonsil biopsy: vCJD only, present in lymphoreticular system (supportive test inly)
PRNP gene analysis (genetic only)
Medical history (iatrogenic obly)
How to manage CJD?
Refer cases to London or Edinburgh
Multi-disciplinary team support management
Management of CJD? Drugs?
Antimicrobial: doxy/tetracycline (increases incubation period, neg clinical trials
Quinacrine: reduces accumulation, unsucess
Chlorpromazine: unsucess
Pentosan polysulphate: IV, unpromising
Management with experimental drug?
PRN100: genetically engineered antibody to bind to the prion protein to stop accumulation
What is the influence of host genotype on susceptibility?
All individuals with vCJD gave a homozygous MM of the prion protein (codon 129)
What are the potential infective tissues? Dental?
High: brain, spinal cord and dura mater
Medium: tonsils, spleen, thymus and other lymphoid tissues
Low: dental pulp, gingival tissues, blood and saliva
Precautionary measures to protect blood products?
Blood components obtained from an individual whom later develops vCJD is withdrawn
Plasma has been obtained non-UK
Synthetic clotting factors for hemophilia
WBCs can pass vCJD, and so reduced in blood by leuco-depletion
Frozen plasma for babies obtained from the US
Individuals whom received a transfusion pre 1980 are excluded from blood donations
Infection control complications of CJD?
Heat resistant
Convention disinfection and sterilisation ineffective
Prions adhere to steel
Importance of scrubbing instruments
Instruments of high or medium risk only reused in same patient
Implication of CJD on dentistry?
The risk of vCJD transmission is low but possible
Instruments specific to patient? In dentistry?
Endodontic files and reamers
