Kathy
Well-known member
Low and behold, another confirmation of manganese and other metals capable of replacing copper on the PrPC protein, and leading to spongiform encephalopathy. To bad these researchers only tested transitional metals.
The evidence is stacking up in Mark Purdey's favour. No doubt these researchers have referenced Dr. DR Brown's work (Bath Univ. UK). Damge from oxidative stress being the main culprit causing neurotoxic damage. Brown's newest paper is entitled:
New support out of France.
The evidence is stacking up in Mark Purdey's favour. No doubt these researchers have referenced Dr. DR Brown's work (Bath Univ. UK). Damge from oxidative stress being the main culprit causing neurotoxic damage. Brown's newest paper is entitled:
Neurodegeneration and oxidative stress: prion disease results from loss of antioxidant defence. Folia Neuropathol. 2005;43(4):229-43.
Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, e-mail: [email protected].
Prion diseases or transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that can be acquired either by direct transmission, inherited through dominant mutations in the prion protein gene or via an unknown sporadic cause. This latter group constitutes the vast majority of cases. Like many neurodegenerative diseases the hallmarks of oxidative damage can be readily detected throughout the brain of the affected individual. However, unlike most other neurodegenerative diseases, prion diseases are connected with a dramatic loss of antioxidant defence. As abnormal protein accumulates in the diseased brain there is both an increase of oxidative substances and a loss of the defences that keep them in check. In particular the normal cellular prion protein has been shown to be an antioxidant. Conversion of this protein to the protease resistant isoform is accompanied by a loss of this antioxidant activity. This change creates a paradox as the loss of activity is not accompanied by a loss of protein expression. It is likely that this prevents other cellular defences from responding sufficiently to protect neurons from the heightened oxidative burden. Recent experiments with transgenic mice have shown that when prion protein expression is switched off during the course of prion disease, cell death is dramatically halted and the mouse recovers from the disease. This result clearly illustrates that the continued expression of non-function prion protein is essential for disease progression. This implies that the presence of this abnormal protein during prion disease causes a failure of cellular antioxidant defence. This failed defence is the fundamental cause of the massive neurodegeneration that results in the fatal nature of TSEs. The role of oxidative stress in TSEs and other neurodegenerative disorders are discussed in this review.
PMID: 16416388
New support out of France.
Neurotoxicology. 2006 Feb 13; [Epub ahead of print]
Free radical generation of protease-resistant prion after substitution of manganese for copper in bovine brain homogenate.
Deloncle R, Guillard O, Bind JL, Delaval J, Fleury N, Mauco G, Lesage G.
Universite Francois Rabelais de Tours, Bio-Inorganic Chemistry Laboratory, Faculty of Pharmacy, 31 Avenue Monge, 37200 Tours, France.
The exchange between copper and seven transition metals is studied in a bovine brain obex homogenate according to the redox status of the medium. In reductive conditions, almost all the studied metals can substitute for copper when it is in the reduced form Cu(+). This substitution is reversible, since copper uptake as Cu(++) is restored in an oxidizing medium but only Co(++), Ni(++) and Mn(++), in this decreasing order, can substitute perfectly for copper in bovine brain homogenate. To study free radical effects on bovine brain proteins, at first a copper substitution was processed in order to inhibit superoxide dismutase-like protective properties against free radicals in copper metalloproteins. Manganese was selected since a brain copper decrease correlated with a manganese increase is well-known in transmissible spongiform encephalopathies. Results for bovine brain homogenate, initially negative in the Western blot Prionics((R)) test, indicate that the substitution of manganese for copper in a reducing medium and exposure to UVA-induced free radicals produce proteinase K resistant prion. These findings suggest that an impairment in brain metal homeostasis leading to oxidative abnormalities may be involved in transmissible spongiform encephalopathies.
PMID: 16481041 [PubMed - as supplied by publisher]