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.
* 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.
* 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?
* 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.
* 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)