Trace Metals
At a time when there
is mounting biochemical evidence for the essential nature of correct trace-element
balance to neuronal activity and resistance to neurodegenerative disease there
is a paucity of research on how trace element dietary status effects livestock
animals.
With threats like TSEs fully in public view it is astounding that the care
of animals and how their diet might expose them to such neurodegenerative
and possibly transmissible diseases is largely ignored. While genetic status
of an animal is an important consideration in this molecular age, it remains
a fact that the phenotype of an animal is what is important and diet remain
the single most critical regulator, aside from genetic information, that determines
what that phenotype will be.
- 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
- 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
- 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
- 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
- Molybdenum toxicity
in cattle: an underestimated problem:
Molybdenum toxicity is a controversial subject. However, much of the contention
is due to inappropriate diagnosis. This paper shows the flaw in using plasma
copper levels alone to diagnose a bolybdenum toxic condition, based on samples
from >7.500 dairy cattle. Telfer
et al
- A Delicate Balance:
Homeostatic Control of Copper Uptake and Distribution:
The cellular uptake and intracellular distribution of the essential but
highly toxic nutrient, copper, is a precisely orchestrated process. Copper
homeostasis is coordinated by several proteins to ensure that it is delivered
to specific subcellular compartments and copper-requiring proteins without
releasing free copper ions that will cause damage to cellular components.
Genetic studies in prokaryotic organisms and yeast have identified membrane-associated
proteins that mediate the uptake or export of copper from cells.
Maria
M.O. Pena
- Copper Binding to
the Octarepeats of the Prion Protein:
The prion protein (PrP) is a Cu2_ binding cell surface glycoprotein. There
is increasing evidence that PrP functions as a copper transporter. In addition,
strains of prion disease have been linked with copper binding. Anthony P.
Garnett and John H. Viles
Copper Converts the Cellular Prion Protein into a Proteaseresistant Species
That Is Distinct from the Scrapie Isoform:
Several lines of evidence have suggested that copper ions play a role in
the biology of both PrPC and PrPSc, the normal and pathologic forms of the
prion protein. Elena
Quaglio et
- Copper Stimulates
Endocytosis of the Prion Protein:
Prion diseases result from conformational alteration of PrPC, a cell surface
glycoprotein expressed in brain, spinal cord, and several peripheral tissues,
into PrPSc, a protease-resistant isoform that is the principal component
of infectious prion particles.
Peter
C. Pauly and David A. Harris
- Electron Paramagnetic
Resonance Evidence for Binding of Cu21 to the C-terminal Domain of the Murine
Prion Protein:
Transmissible spongiform encephalopathies in mammals are believed to be
caused by scrapie form of prion protein (PrPSc), an abnormal, oligomeric
isoform of the monomeric cellular prion protein (PrPC). One of the roposed
functions of PrPC in vivo is a Cu(II) binding activity. Grazia
M. Cereghetti et al
- Ionic Strength and
Transition Metals Control PrPSc Protease Resistance and Conversion-inducing
Activity:
The essential component of infectious prions is a misfolded protein termed
PrPSc, which is produced by conformational change of a normal host protein,
PrPC. It is currently unknown whether PrPSc molecules exist in a unique
conformation or whether they are able to undergo additional onformational
changes.
Koren Nishina et al
- Mayhem of the multiple
mechanisms: modelling neurodegeneration in prion disease:
This review examines recent attempts to advance the understanding of the
mechanism by which neurones die in prion disease.
David
R. Brown
- Metal Toxicity and
Therapeutic Intervention:
Copper and prion diseases D.R.Brown
- Myocardial cytochrome
c oxidase activity in Swedish moose (Alces alces L.) affected by molybdenosis.
Since the mid-19809s, a ‘mysterious’ wasting disease has been
afflicting the moose population of south-western Sweden. In 1994 molybdenosis
combined with copper deficiency was suggested as the cause of this complex
syndrom of clinical signs, diversity of necropsy findings and changes in
trace element concentrations.
Adrian Frank
disclamer
