Prion Disorder Research Paper
The Elusive Prions and CJD: possible to treat?
Introduction to Prion Disease
Prion disease is an infectious neurodegenerative disease caused by a naturally occurring protein (PrPC) misfolding into an aberrant form
(PrPSC) which aggregates and destroys neuronal tissue. PrPSC was originally posited by Stanley Prusiner to be the sole causative moiety in prion disease (Prion Theory), however there is some evidence to suggest that unknown toxic intermediates, co-factors, and certain nucleic acids may have roles to play in its pathogenesis. In humans the diseases are named Creutzfeldt-Jakob Disease (CJD), GerstmannSträussler-Scheinker (GSS) syndrome, Fatal Familial Insomnia (FFI) and kuru. These conditions differ in aetiology, the cause …show more content…
As of yet there is no effective cure. The incubation times of prion diseases are usually long (years), but once clinically apparent are rapidly progressive.
Resistance to treatment & current approaches The disease-causing moiety, whether protein-only or not, is remarkably resistant to a myriad of physical , chemical and biological treatments and retains infectivity after:
• Irradiation with UV light
• Nucleases
• Hydrolysis
• Bleach
• Intense heat of 132*C for 30 minutes
Research Proposal: Lichens – natural born prion killers? Lichens are composite symbiotic organisms consisting of a fungus and a photosynthetic organism (usually algae or a cyanobacteria).
Current approaches to therapy :
•
Image showing the spongiform changes found in brains of prion disease-affected individuals.
CJD
Sporadic CJD (sCJD) – the seemingly ‘random’ conversion of normal
Inhibition of PrPC synthesis (prion replication requires the presence of normal cellular PrP as a template) • Stabilising PrPC conformation
• Enhancing PrPSC clearance
• Preventing PrPSC …show more content…
Recently (2011) a paper was published by Christopher J. Johnson et al who discovered species of lichen that effectively degrade PrPC and PrPSC in vitro.
By mixing infected and control brain homogenates with lichen extracts, they showed significantly reduced immunoreactivity of the PrP protein when precipitated with a PrP-specific antibody. The authors further showed that the likely agent causing this degradation was a serine-protease.
Variant CJD (vCJD) – In the UK, in 1996, vCJD was described, caused by bovine spongiform encephalopathy (BSE) found in cattle. It was thought to be transmitted to humans through the consumption of affected meat.
The mean age of presentation is approximately 19-37 years, normally showing a longer duration of illness than sCJD.
Familial CJD – autosomal dominant PrP gene mutations leading to the increased propensity for PrPC to misfold into PrPSC. This form of CJD is inherited. Codon 129 of PRNP gene often affects the phenotype.
Iatrogenic CJD – transmitted by PrPSC-contaminated medical equipment. A notable instance in the UK regarding human growth hormone treatment in children, whereby the isolates used contained
PrPSC from affected individuals.
Introduction to Prion Disease
Prion disease is an infectious neurodegenerative disease caused by a naturally occurring protein (PrPC) misfolding into an aberrant form
(PrPSC) which aggregates and destroys neuronal tissue. PrPSC was originally posited by Stanley Prusiner to be the sole causative moiety in prion disease (Prion Theory), however there is some evidence to suggest that unknown toxic intermediates, co-factors, and certain nucleic acids may have roles to play in its pathogenesis. In humans the diseases are named Creutzfeldt-Jakob Disease (CJD), GerstmannSträussler-Scheinker (GSS) syndrome, Fatal Familial Insomnia (FFI) and kuru. These conditions differ in aetiology, the cause …show more content…
As of yet there is no effective cure. The incubation times of prion diseases are usually long (years), but once clinically apparent are rapidly progressive.
Resistance to treatment & current approaches The disease-causing moiety, whether protein-only or not, is remarkably resistant to a myriad of physical , chemical and biological treatments and retains infectivity after:
• Irradiation with UV light
• Nucleases
• Hydrolysis
• Bleach
• Intense heat of 132*C for 30 minutes
Research Proposal: Lichens – natural born prion killers? Lichens are composite symbiotic organisms consisting of a fungus and a photosynthetic organism (usually algae or a cyanobacteria).
Current approaches to therapy :
•
Image showing the spongiform changes found in brains of prion disease-affected individuals.
CJD
Sporadic CJD (sCJD) – the seemingly ‘random’ conversion of normal
Inhibition of PrPC synthesis (prion replication requires the presence of normal cellular PrP as a template) • Stabilising PrPC conformation
• Enhancing PrPSC clearance
• Preventing PrPSC …show more content…
Recently (2011) a paper was published by Christopher J. Johnson et al who discovered species of lichen that effectively degrade PrPC and PrPSC in vitro.
By mixing infected and control brain homogenates with lichen extracts, they showed significantly reduced immunoreactivity of the PrP protein when precipitated with a PrP-specific antibody. The authors further showed that the likely agent causing this degradation was a serine-protease.
Variant CJD (vCJD) – In the UK, in 1996, vCJD was described, caused by bovine spongiform encephalopathy (BSE) found in cattle. It was thought to be transmitted to humans through the consumption of affected meat.
The mean age of presentation is approximately 19-37 years, normally showing a longer duration of illness than sCJD.
Familial CJD – autosomal dominant PrP gene mutations leading to the increased propensity for PrPC to misfold into PrPSC. This form of CJD is inherited. Codon 129 of PRNP gene often affects the phenotype.
Iatrogenic CJD – transmitted by PrPSC-contaminated medical equipment. A notable instance in the UK regarding human growth hormone treatment in children, whereby the isolates used contained
PrPSC from affected individuals.