Coenzyme Q and protein/lipid oxidation in a BSE-infected transgenic mouse model

Martín, Sergio F.; Burón, Isabel; Espinosa, Juan Carlos; Castilla, Joaquı́n; Villalba, José M.; Torres, Juan María

doi:10.1016/j.freeradbiomed.2007.03.005

Cited by 32 publications

(19 citation statements)

References 62 publications

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“…As previously shown in the same model [66,67] and in a wild type murine model [10] cellular and oxidative stress seem to play a significant role in the outcome of BSE. Additional evidence of this is provided by the results of the present experiment, namely by an upregulation of HSPB6 (HSP20) and Mt2 at 270 dpi (see Table 1).…”

Section: Discussionsupporting

confidence: 61%

Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

Tortosa

Castells

Vidal

et al. 2011

Vet Res

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Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations.

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Section: Discussionsupporting

confidence: 61%

Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

Tortosa

Castells

Vidal

et al. 2011

Vet Res

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“…We thus conclude that PrP sc may affect Dab1 phosphorylation and A production. PrP sc inoculation gives rise to a wide range of molecular responses in infected brains (Xiang et al, 2004) including in oxidative stress (Choi et al, 1998;Martin et al, 2007;Yun et al, 2006), which is also described in sCJD patients (Freixes et al, 2006;Pamplona et al, 2008;Petersen et al, 2005). Indeed, sCJD patients with PrP sc type 1 and MM polymorphism at codon 129 are characterized by faster evolution and decreased life expectancy compared with PrP sc type 2 with other polymorphisms at codon 129 (Uro-Coste et al, 2008).…”

Section: Discussionmentioning

confidence: 98%

Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Gavı́n¹,

Ferrer²,

Rı́o³

2010

Neurobiology of Disease

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Alzheimer's disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of Amyloid Precursor Protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in seventeen cases of sporadic CJD (sCJD) post mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrP sc types 1 and 2. One group, with PrP sc type 1 showed increased Dab1 phosphorylation, and lower CTF production with an absence of A deposition. The second sCJD group, which carried PrP sc type 2, showed lower levels of Dab1 phosphorylation and CTF production, and A deposition. Thus, the present observations suggest a correlation between Dab1-phosphorylation, A deposition and PrP sc type in sCJD.

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“…Later, the ability of a polyclonal serum (raised against PrP sequence [219][220][221][222][223][224][225][226][227][228][229][230][231][232] to interact with PrP c and inhibit cell-free conversion [57] suggested that antibodies might be good treatment candidates. Enari et al then discovered that PrP antibody 6H4 was able to cure chronically infected neuroblastoma cells [58].…”

Section: A Role For Antibodiesmentioning

confidence: 99%

“…Cells without PrP c are more sensitive to oxidative stress [214,218,219], and increased oxidative stress is seen in infected animals [220,221]. Brain levels of coenzyme Q 9 and Q 10 , endogenous lipophilic antioxidants, steadily increased in BSE-infected mice expressing bovine PrP c , beginning at the time PrP res deposits began to appear (150 days post-inoculation) [222]. This suggests that the antioxidant system is not only active in prion disease, but may be overwhelmed.…”

Section: Antioxidantsmentioning

confidence: 99%