Bovine Spongiform Encephalopathy
- A field on fire;
The biochemistry of mad cows:
Prion diseases are neurodegenerative diseases1 that have been linked together
because they may potentially have the same cause.These include the diseases
scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and
also several human diseases that include sporadic CJD (Creutzfeldt-Jakob)
disease and a variety of inherited forms. David
R. Brown
- TSE roadmap:
The Commission (EU) has discussed on several occasions with the Member States
and the European Parliament about the next steps in the BSE policy on different
points such as the definition and removal of Specified Risk Material (SRM),
the feed ban and the age of testing. Based on the improved situation, the
Commission has taken this initiative to present a roadmap on the BSE strategy
in the short, medium and long-term. TSE
road map
- Consequences of
Manganese replacement of Copper for prion protein function and proteinase
resitance:
The pron protein (PrP) binds copper and has antioxidant activity enhancing
the survival of neurones in culture: Brown
et al
- BSE in sheep bred
for resistance to infection:
Selective breeding for disease-resistant genotypes is being pursued as a
means of eradicating scrapie (and BSE, if it is present) from sheep flocks.
Here we show that the genotype associated with the highest resistance can
still be infected with BSE by intracerebral inoculation: Fiona
Houston et al
- Review of the origin
of BSE:
To assess the current state of understanding of the origin of BSE, taking
into account the scientific and epidemological evidence presented to the
BSE Inquiry, the findings of the Working Group of the EU's Scientific Steering
Committee, and any recently published or ongoing work being undertaken in
the UK or elswhere. Horn
- A case for the role
of copper deficiency in "mad-Cow"disease and human Creutzfeld-Jakob
disease:
It has been recognized for centuries that copper plays a vital role in medicine.
Since 1928 we have also known that copper is an essential element in human,
animal and plant nutrition. It has recently been suggested that copper also
affects a newly indentified class of ailmanets known as prion diseases.
Dresher et al
- Copper chelation
delays the onset of prion disease:
The prion protein (PrP) binds copper and under some conditions copper can
facilitate its folding into a more protease resistant form. Hence, copper
levels may influence the infectivity of the scrapie form of prion protein
(PrPsc). Sigurdsson
et al
- Discuss a re-evaluation
of the TSE enigma and explore the role of environmental factors in prion
diseases:
Despite extensive research and an equally wide-ranging BSE Public Inquiry
chaired by Lord Phillips, there is much that is unanswered or mainly speculative
and it is time for a re-evaluation of the collated information, together
with more recent investigations shich have an important bearing on the pathogenesis
on the unique class of diseases. Brown
& Haywood
- Mayhem of the multiple
mechanisms: modelling meurodegeneration in prion disease:
This revew examines recent attempts to advance the understanding of the
mechanism by which neurones die in prion disease. Brown
BSE did not cause variant CJD: an alternative cause related to post-industrial
environmental contamination:
The new prion diseases that have emerged in the last 15 years are BSE and
variant CJD. Although initially confined to the UK, thesse diseases have
emerged in other European countries. The accepted cause of the human disease
is that BSE spread from cattle to humans by the consumption of infected
beef. However, the evidence that supports this is very thin. Brown
- Aberrant metal binding
by prion protein in human prion disease:
Human prion diseases are characterized by the conversion of the normal protein
(PrPc) into a pathogenic isomer (PrPSc). Distinct PrPSc conformers are associated
with different subtypes of prion diseases. PrPC binds copper and has antioxidation
activity. Changes in metal-ion occupancy can lead to significant decline
of the antioxidation activity and changes in conformation of the protein.
Wong
et al
- Exuberant cellular
reaction of the optic nerves in experimental Creutzfeldt-Jakob disease:
We report here on the exuberant glial reaction in the optic nerves affected
by prion diseases. Optic nerves from CJD-and GSS-, and scrapie-infected
mice and hamsters showed severe pathology. These lesions were qualitatively
indistinguishable from each other but were more intense in the Fujisaki
model than in the hamsters inoculated with Echigo-1. Liberski
et al
- Prions shwo their
metal:
Ian Jones describes the evidence that increasingly links prion proteins
and copper ions. Could a defect in the metabolism of this simple metal be
at the heart of 'mad cow' disease? Jones
- Metal imbalance
and compromised antioxidant function are early changes in prion disease:
The prion protein (PrP) has been shown to bind copper. In the present study
we have investigated whether prion disease in a mouse scrapie model resulted
in modifications of metal concentrations. We found changes in the levels
of copper and manganese in the brains of scrapie-infected mice prior to
the onset of clinical symptoms. Interestingly, we noted a major increase
in blood manganese in the early stages of disease. Thackray
et al
- The structure function
relationship for the Prion protein:
Central to Prion diseases is the normal endogenous Prion protein, PrPC.
In spite of years of research the exact function of this protein remains
enigmatic. Numerous binding partners have been identified for PrPC and due
to the presence of a repeated sequence of PHGGGWGQ in the proteins amino-terminus
it can bind metal ions. Deignan
et al
- Trace element (nutritional)
theory of 'mad cow' disease:
Even if the prion-only theory of BSE proves to be substantially correct,
copper and other trace metals may have a key role in controlling infectivity
of this molecule. It now appears that the normal prion protein (PrP) of
nerve cells in the brain could have a key role in the critical functions
of copper in the brain.
McBride
- BSE AND SHEEP: CURRENT
KNOWLEDGE, RISK ASSESSMENT, SRM CONTROLS AND OPTIONS
Department of Infectious and Tropical Diseases London School of Hygiene
& Tropical Medicine Chair, Spongiform Encephalopathy Advisory Committee
(SEAC) Peter Smith
disclamer
