BSE did not cause variant CJD: an alternative cause related to post-industrial environmental contamination

Brown, David R.

doi:10.1054/mehy.2001.1388

Cited by 12 publications

(5 citation statements)

References 25 publications

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“…We used the GAMM v1.4 software [41] to perform a Mixed Model Analysis using a Bayesian approach that allowed the establishment of associations between gene expression data and prion deposition, gliosis and spongiosis. The spongiosis, PrP Sc deposits and generalized reactive gliosis observed in the medulla oblongatas of scrapie-affected animals in the present study were in accordance with previous descriptions of classical scrapie [31], [70], [71], [72], [73] and support the hypothesis that PrP Sc deposition elicits a responsive glial cell proliferation and the appearance of spongiotic lesions [15], [74], [75], [76]. The increase of GFAP in affected animals was in accordance with the microarray experiment results, in which the GFAP gene was upregulated in scrapie medullae with a 1.7-fold change (data not shown in Table S1 because only genes with a FC>2 are represented).…”

Section: Discussionsupporting

confidence: 93%

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Filali

Martín-Burriel

Harders³

et al. 2011

PLoS ONE

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The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.

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Section: Discussionsupporting

confidence: 93%

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Filali

Martín-Burriel

Harders³

et al. 2011

PLoS ONE

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“…Similarly to AD, the role of environmental risk factors for human prion diseases remain largely unknown, although a role for alimentary copper deficiency and increased intake of Al and manganese has been advanced for animal TSE [51]. In addition, a role for exposure to fertilizer and gardening products containing bone meal products of infected animals has been suggested [52].…”

Section: Environmental Causes and Alimentary Exposure: Tales Of Metalmentioning

confidence: 99%

Cerebral Amyloidoses: Molecular Pathways and Therapeutic Challenges

Monaco

Zanusso²,

Mazzucco³

et al. 2006

CMC

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Alzheimer disease (AD) and Creutzfeldt-Jakob disease (CJD) are sporadic and genetic neurodegenerative conditions characterized by brain accumulation and deposition of protein aggregates. In AD, the key pathogenic event is linked to the formation of a 4-kDa amyloid beta (Abeta) peptide, generated by sequential cleavages of the amyloid precursor protein (APP). In CJD and other prion diseases, the process is initiated by conformational changes of the cellular prion protein, or PrP(C), into a beta-sheet rich isoform, named PrP(Sc), which acquires protease-resistance and detergent insolubility. Once generated, Abeta and PrP(Sc) are highly prone to misassembly under thermodynamically favourable oligomeric forms and protofibril/fibril structures. The variety of physicochemical states exhibited by Abeta and PrP(Sc) is accounted for by distinct molecular forms with different amino and/or carboxyl termini and alternative conformations. Unlike Abeta, PrP(Sc) is also infectious, and this feature poses public health concerns, as in the case of iatrogenic and variant CJD (vCJD). Several lines of evidence suggest that Abeta and PrP(Sc) are the main factors responsible for death of selected neuronal populations in brains of AD and prion disease's victims. Therefore, in addition to symptomatic treatment of dementia, therapeutic efforts are currently aimed at testing the efficacy of disease-modifying, anti-amyloid therapies. Experimental and clinical therapeutic interventions include passive and active immunization against amyloidogenic peptides, non immunological strategies, as well as drugs enhancing the nonamyloidogenic protein processing. In this review, we focus on molecular mechanisms of AD and prion diseases, and on novel treatment approaches.

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“…Lesions associated with TSEs are influenced by intracellular stress, which may be caused by changes in some metal concentrations [7,8]. Oxidative damage and apoptosis have been well documented in animal and human prion diseases [9–11].…”

Section: Introductionmentioning

confidence: 99%

Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie

Bolea

Hortells

Martín-Burriel

et al. 2010

Neuropathology Appl Neurobio

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With regard to apoptosis induction, the response of Tga20 mice to prion infection was similar to that reported for other mice models. Our results demonstrate the neuroprotective effects of -Cu, -Cu+Mn and +Mn diets in a murine model of scrapie. However, neuronal death induced by infection with prions seems to be independent of apoptosis marker signalling. Moreover, copper-modified diets were neuroprotective against the possible toxicity of the prion transgene in Tga20 control and infected mice even though manganese supplementation could not counteract this toxicity.

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BSE did not cause variant CJD: an alternative cause related to post-industrial environmental contamination

Cited by 12 publications

References 25 publications

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Cerebral Amyloidoses: Molecular Pathways and Therapeutic Challenges

Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie

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