An integrated map of the murine hippocampal proteome based upon five mouse strains

Pollak, Daniela D.; John, Julius Paul Pradeep; Hoeger, Harald; Lubec, Gert

doi:10.1002/elps.200500648

Cited by 22 publications

(9 citation statements)

References 21 publications

(25 reference statements)

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“…Information was collected from the European Molecular Biology Laboratory-European Bioinformatics Institute and Swiss-Prot databases. Relative numbers (%) are presented, and these are compared with the results of a previous study (data within parentheses) of the proteome of murine CNS (18). each group.…”

Section: Resultsmentioning

confidence: 99%

Changes in the Spinal Cord Proteome of an Amyotrophic Lateral Sclerosis Murine Model Determined by Differential In-gel Electrophoresis

Bergemalm

Forsberg

Jonsson

et al. 2009

Molecular & Cellular Proteomics

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons resulting in progressive paralysis. To date, more than 140 different mutations in the gene encoding CuZn-superoxide dismutase (SOD1) have been associated with ALS. Several transgenic murine models exist in which various mutant SOD1s are expressed. We used DIGE to analyze the changes in the spinal cord proteome induced by expression of the unstable SOD1 truncation mutant G127insTGGG (G127X) in mice. Unlike mutants used in most other models, G127X lacks SOD activity and is present at low levels, thus reducing the risk of overexpression artifacts. The mice were analyzed at their peak body weights just before onset of symptoms. Variable importance plot analysis showed that 420 of 1,800 detected protein spots contributed significantly to the differences between the groups. By MALDI-TOF MS analysis, 54 differentially regulated proteins were identified. One spot was found to be a covalently linked mutant SOD1 dimer, apparently analogous to SOD1-immunoreactive bands migrating at double the molecular weight of SOD1 monomers previously detected in humans and mice carrying mutant SOD1s and in sporadic ALS cases. Analyses of affected functional pathways and the subcellular representation of alterations suggest that the toxicity exerted by mutant SODs induces oxidative stress and affects mitochondria, cellular assembly/organization, and protein degradation. Molecular & Cellular Proteomics 8: 1306 -1317, 2009. Amyotrophic lateral sclerosis (ALS)1 is a devastating neurodegenerative disease characterized by loss of motor neurons in the motor cortex, the brainstem, and the spinal cord. This results in progressive muscular atrophy, and the patients usually succumb to respiratory failure within a few years. About 10% of ALS cases are familial (1), and in some patients the disease is linked to mutations in the CuZn-superoxide dismutase (SOD1) gene (2). SOD1 is a ubiquitously expressed antioxidant enzyme. Overall about 6% of all cases with ALS show SOD1 mutations, and more than 140 such mutations have been identified (3). The mutations confer a cytotoxic gain of function of unknown character to the enzyme (4, 5). ALS caused by mutant SOD1s shows the same spectrum of disease phenotypes as is seen in sporadic cases lacking such mutations. This suggests that the pathogenesis of ALS induced by SOD1 mutations should show significant similarities with that in sporadic disease, e.g. similar pathogenic protein alterations.ALS has been modeled in mice via transgenic overexpression of mutant SOD1s (5-8). To cause disease within the short lifespan of a mouse, the mutant SOD1s have to be expressed at rates around 25-fold higher than the rate of expression of the endogenous murine enzyme (9). Mostly structurally stable mutants have been used, resulting in up to 10-fold increases in SOD activity and 20-fold increases in SOD1 protein levels in the CNS that may cause overexpression artifacts. Overloading of mitochondria with mutant SOD1s...

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Section: Resultsmentioning

confidence: 99%

Changes in the Spinal Cord Proteome of an Amyotrophic Lateral Sclerosis Murine Model Determined by Differential In-gel Electrophoresis

Bergemalm

Forsberg

Jonsson

et al. 2009

Molecular & Cellular Proteomics

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“…Proteomics has been widely used in neuroscience and particularly for comparison between healthy individuals and patients suffering from neurodegenerative or other diseases influencing the central nervous system (20), (21) as well as for mapping of proteins in hippocampus to study functions in the central nervous system (22), (23), (24). …”

Section: Proteomicsmentioning

confidence: 99%

Prefractionation of Cerebrospinal Fluid to Enhance Glycoprotein Concentration Prior to Structural Determination with FT−ICR Mass Spectrometry

2005

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När vi leva, låtom oss leva. While we live, let us live. "Let us enjoy life." Dum vivimus vivamus.3 Mass spectrometry for comparative proteomics of degenerative and regenerative processes in the brain ABSTRACT Biological processes involve changes at the protein level which can be detected and quantified. Proteomics aims to determine protein changes from a normal state, for instance to measure the degree of recovery in a biological system or the state of disease progression. Mass spectrometry is the most important tool in proteomics for the identification of proteins and determination of post-translational modifications such as glycosylation. Glycoproteins were found to be altered in patients with Alzheimer's disease (AD), which is the most common form of dementia. Changes in glycosylation levels were quantified with a glycoprotein-specific stain after gel separation. Glycan structures were determined with mass spectrometry in this thesis. Protein quantification with mass spectrometric methods is based on stable isotope labeling of proteins and labeled cell cultures can be used as internal standards for tissue proteomics. Quantitative proteomics was applied to assess protein expression levels with mass spectrometry in the murine brain after specific neurosurgery to study regenerative processes.In order to compare glycosylated proteins in cerebrospinal fluid (CSF) from individual AD patients with healthy control individuals, glycoproteomic methods were developed. To enhance the concentration of glycoproteins prior to gel separation, affinity chromatography of CSF was the most suitable prefractionation method for removing the most abundant CSF protein albumin. CSF proteins were separated with narrow pH-range two-dimensional gel electrophoresis followed by multiple staining for quantification of glycoprotein isoforms. Structural analysis of glycopeptides was performed with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), which provided very high mass accuracy and facilitated site-specific determination. A decreased glycosylation level for a protein localized in senile plaques, α 1 -antitrypsin, was found in AD patients. No specific glycoform of the studied proteins could be assigned to AD, emphasizing that further studies should include a larger subject group and cover proteins in various pH intervals. Knowledge of the respective glycoprotein structures in relation to clinical disease parameters may assist in the elucidation of the pathogenesis.In order to study proteins involved in the response of astrocytes and regenerative processes after neurotrauma, a quantitative mass spectrometric method was developed. Astrocytes, which are the most abundant cells in the central nervous system, react to neurotrauma by becoming reactive (reactive gliosis). Mice lacking the intermediate filament proteins GFAP and vimentin (GFAP -/-Vim -/-) show attenuated reactive gliosis and enhanced regeneration after neurotrauma. Comparative proteomic analysis showed upregulation of the adapter protein 14-3-3 in wildt...

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“…There were 469 individual proteins in the reference database that displayed various functional states of the respective gene products, providing a pivotal role for neuronal information processing and storage [53].…”

Section: Proteomics Of the Brain In Different Animalsmentioning

confidence: 99%

Proteomic Studies on the Development of the Central Nervous System and Beyond

Zhang

2010

Neurochem Res

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Neuroproteomics has become a 'symbol' or even a 'sign' for neuroscientists in the post-genomic era. During the last several decades, a number of proteomic approaches have been used widely to decipher the complexity of the brain, including the study of embryonic stages of human or non-human animal brain development. The use of proteomic techniques has allowed for great scientific advancements, including the quantitative analysis of proteomic data using 2D-DIGE, ICAT and iTRAQ. In addition, proteomic studies of the brain have expanded into fields such as subproteomics, synaptoproteomics, neural plasma membrane proteomics and even mitochondrial proteomics. The rapid progress that has been made in this field will not only increase the knowledge based on the neuroproteomics of the developing brain but also help to increase the understanding of human neurological diseases. This paper will focus on proteomic studies in the central nervous system and especially those conducted on the development of the brain in order to summarize the advances in this rapidly developing field.

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An integrated map of the murine hippocampal proteome based upon five mouse strains

Cited by 22 publications

References 21 publications

Changes in the Spinal Cord Proteome of an Amyotrophic Lateral Sclerosis Murine Model Determined by Differential In-gel Electrophoresis

Changes in the Spinal Cord Proteome of an Amyotrophic Lateral Sclerosis Murine Model Determined by Differential In-gel Electrophoresis

Prefractionation of Cerebrospinal Fluid to Enhance Glycoprotein Concentration Prior to Structural Determination with FT−ICR Mass Spectrometry

Proteomic Studies on the Development of the Central Nervous System and Beyond

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