Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis

Sizova, Daria; Charbaut, Elodie; Delalande, François; Poirier, Florence; High, Anthony A.; Parker, Fabienne; Dorsselaer, Alain Van; Duchesne, Marc; Diu-Hercend, Anita

doi:10.1016/j.neurobiolaging.2006.01.011

Cited by 45 publications

(43 citation statements)

References 58 publications

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“…In addition, increased Prx1 expression has been detected in brain tissue from a Huntington disease and prion mouse model (40). Proteomic analysis of cortical tissue from an AD mouse model revealed increased Prx6 expression in older transgenic (tg) animals compared with non-tg littermates (41). Collectively, these findings indicate that increased Prx expression is associated with amyloidgenic diseases.…”

Section: Discussionmentioning

confidence: 89%

Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

Cumming

Dargusch

Fischer

et al. 2007

Journal of Biological Chemistry

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Peroxiredoxins (Prxs) are a ubiquitously expressed family of thiol peroxidases that reduce hydrogen peroxide, peroxynitrite, and hydroperoxides using a highly conserved cysteine. There is substantial evidence that oxidative stress elicited by amyloid ␤ (A␤) accumulation is a causative factor in the pathogenesis of Alzheimer disease (AD). Here we show that A␤-resistant PC12 cell lines exhibit increased expression of multiple Prx isoforms with reduced cysteine oxidation. A␤-resistant PC12 cells also display higher levels of thioredoxin and thioredoxin reductase, two enzymes critical for maintaining Prx activity. PC12 cells and rat primary hippocampal neurons transfected with wild type Prx1 exhibit increased A␤ resistance, whereas mutant Prx1, lacking a catalytic cysteine, confers no protection. Using an antibody that specifically recognizes sulfinylated and sulfonylated Prxs, it is demonstrated that primary rat cortical nerve cells exposed to A␤ display a time-dependent increase in cysteine oxidation of the catalytic site of Prxs that can be blocked by the addition of the thiol-antioxidant N-acetylcysteine. In support of previous findings, expression of Prx1 is higher in post-mortem human AD cortex tissues than in age-matched controls. In addition, two-dimensional gel electrophoresis and mass spectrometry analysis revealed that Prx2 exists in a more oxidized state in AD brains than in control brains. These findings suggest that increased Prx expression and resistance to sulfhydryl oxidation in A␤-resistant nerve cells is a compensatory response to the oxidative stress initiated by chronic pro-oxidant A␤ exposure.A wide body of evidence has implicated oxidative damage in the pathogenesis of Alzheimer disease (AD) 3 (1). AD, the most common form of dementia in the elderly, is characterized by extracellular neuritic plaques containing the amyloid beta (A␤) peptide 1-42 and intracellular neurofibrillary tangles composed mainly of hyperphosphorylated tau protein. Several studies have shown that A␤ exposure increases levels of hydrogen peroxide (H 2 O 2 ), lipid peroxidation, and protein oxidation (carbonylation) in cultured neurons (2-4). Increased oxidative damage to lipids, DNA, and proteins is also found in AD brains (1). Because the exogenous addition of antioxidants or catalase protects cultured nerve cells from A␤ toxicity (2, 5), it is likely that free radicals play a critical role in A␤ cytotoxicity. Therefore, cellular mechanisms that either prevent or remove reactive oxygen species (ROS) or reverse damage to cellular components after ROS exposure may play a key role in blocking A␤ toxicity. Although widespread nerve cell death occurs in the brains of AD patients, some neurons are spared, indicating that certain populations of cells survive the same conditions that kill neighboring cells. Early studies had shown that low concentrations of A␤ can actually rescue neurons from stressful conditions (6). However, the mechanism of A␤ resistance is only poorly understood. Previously, a series of A␤-resistant clones w...

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Section: Discussionmentioning

confidence: 89%

Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

Cumming

Dargusch

Fischer

et al. 2007

Journal of Biological Chemistry

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“…Genome multiplication in mammals has been associated with alterations in a wide range of cellular processes, including enhanced protein turnover and transcriptional rate, shift from aerobic to anaerobic metabolism, and stress response. 130,131 Interestingly, neurons expressing Swedish mutant APP, known to trigger re-entering into the cell cycle, 37,38 show extensive alterations in gene expression including those involved in energy metabolism, nucleotide and protein synthesis, and oxidative stress, [132][133][134] suggesting that these changes in gene expression may be linked to tetraploidization. Transcription may also be altered at advanced stages of AD, when neurons show active cdc2/cyclin B1, since RNA polymerase II becomes phosphorylated by this kinase.…”

Section: A Model For Ad Based On Neuronal Tetraploidizationmentioning

confidence: 99%

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75^NTR

Frade

López-Sánchez²

2010

Cell Cycle

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“…Especially promising is the measurement of antecedent molecular biomarkers in cerebrospinal fluid (CSF) that will identify those presymptomatic individuals with MCI who will convert to AD. Such molecular biomarkers which also reflect the neuropathology and are modifiable by treatment would provide invaluable support for disease modification claims [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Proteomic approaches are now widely used in the investigation of neurodegenerative diseases and, in particular, as a nonbiased quantification approach for the detection of differences in global patterns of proteins and peptides between healthy and diseased individuals [6][7][8][9][10][11][12][13]. One of the driving forces of proteomics in drug development is the discovery of biomarker candidates of potential clinical relevance in the periphery [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of Cerebrospinal Fluid by 8-Plex iTRAQ Reveals Potential Biomarker Candidates of Alzheimer’s Disease

Guerreiro

Gomez‐Mancilla

Williamson³

et al. 2009

Clin Proteom

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Introduction Alzheimer’s disease (AD) poses specific challenges for drug development. It has a slow and variable clinical course, an insidious onset, and symptom expression is only observed when a significant proportion of neurons are already lost. Discussion Determinants of clinical course, such as molecular biomarkers, are urgently needed for early detection and diagnosis, or for prognosis and monitoring disease-modifying therapies in stratified patient populations. Due to its proximity to the brain and clinical availability, cerebrospinal fluid (CSF) is likely to have the highest yield of biomarker potential for neurodegenerative diseases. In this study, we examined the feasibility of using of an 8-plex isobaric tagging approach, coupled to two-dimensional liquid chromatography and tandem mass spectrometry using the matrix-assisted laser desorption/ionization time-of-flight/time-of-flight platform, for the discovery of potential biomarker candidates in CSF. Comparative analysis identified a number of statistically significant differences in the level of proteins when comparing AD to nondemented controls. Although the study is statistically underpowered to represent the disease population, the regulation of proteins with involvement in processes such as neuronal loss, synaptic dysfunction, neuroinflammation, and tissue degeneration and remodeling reflects the ability of our method in providing biologically meaningful CSF biomarkers as candidates for larger scale biomarker verification and validation studies.

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Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis

Cited by 45 publications

References 58 publications

Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75^NTR

Proteomic Profiling of Cerebrospinal Fluid by 8-Plex iTRAQ Reveals Potential Biomarker Candidates of Alzheimer’s Disease

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Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis

Cited by 45 publications

References 58 publications

Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

Increase in Expression Levels and Resistance to Sulfhydryl Oxidation of Peroxiredoxin Isoforms in Amyloid β-Resistant Nerve Cells

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75NTR

Proteomic Profiling of Cerebrospinal Fluid by 8-Plex iTRAQ Reveals Potential Biomarker Candidates of Alzheimer’s Disease

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A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75^NTR