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Results for “brain proteomics”

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At least 469 records · Page 26Linked to original sources
PubMed2003

Magnetic resonance image-guided proteomics of human glioblastoma multiforme.

PURPOSE: To investigate the correlation between gadolinium contrast-enhancement patterns on T1-weighted magnetic resonance (MR) images and spatial changes in protein expression profiles in human glioblastoma multiforme (GBM) and the use of imaging as a noninvasive technique to evaluate the heterogeneity of solid tumors prior to microarray analysis. MATERIALS AND METHODS: Four patients with MR images and confirmed diagnosis of GBM were enrolled in the study. Intraoperative stereotaxy was used in conjunction with MR images to identify contrast-enhanced (CE) and nonenhanced (NE) regions of the tumor during surgical resection. Total protein was extracted from resected tumor samples using standard techniques and subjected to proteomic analysis using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS). RESULTS: We found that protein profiles from CE and NE regions within a given tumor have qualitative and semiquantitative proteomic pattern differences, suggesting an altered gene expression profile that correlates with detectable tissue imaging parameters. We also found that CE regions within the same tumor exhibited distinct differences in protein expression profiles, despite similar histological features. In addition, there were marked similarities in the proteomic patterns among the NE regions across all patients, while the CE regions were distinct, suggesting that the CE regions have complex protein profiles unique to individuals. CONCLUSION: The results demonstrate that major differences in protein expression patterns within a tumor can be correlated to radiographic findings. Image-guided proteomics holds promise for characterizing tissue prior to microarray analysis designed to identify specific diagnostic markers and therapeutic targets within solid tumors.

Brain Neoplasms↗
PubMed2004

Glycosylation changes in Alzheimer's disease as revealed by a proteomic approach.

Glycosylation influences the biological activity of proteins and affects their folding and stability. Because aberrant glycosylation is associated with Alzheimer's disease (AD), we applied proteome analysis together with Pro-Q Emerald 300 glycoprotein staining to investigate changes in glycosylated cytosolic proteins in AD and control brain. Frontal cortex proteins from 10 AD patients and 7 non-demented controls were subjected to separation by two-dimensional gel electrophoresis and subsequently stained with carbohydrate-specific Pro-Q Emerald 300 dye. Changes in glycosylation of separated proteins were quantified, and proteins of interest identified by mass spectrometry. Approximately 30% of all detectable proteins in the human frontal cortex appeared glycosylated, including heat shock cognate 71 stress protein and beta isoform of creatine kinase. The glycosylation of collapsin response mediator protein 2 (CRMP-2) and an unknown protein was reduced in AD, while the glycosylation of glial fibrillary acidic protein was increased. CRMP-2 regulates the assembly and polymerization of microtubules and is associated with neurofibrillary tangles in AD. Aberrant glycosylations in AD may help understand the mechanisms of neurodegenerative diseases.

Aged↗
PubMed2002

[Proteomics in clinical enzymology: polymorphism of creatine kinase and alkaline phosphatase].

INTRODUCTION: The clinical proteomics is dedicated to the use of the proteomics in the clinical laboratory science. AIMS: Examples for the importance of clinical proteomics are provided by studies on the polymorphisms of creatine kinase and alkaline phosphatase enzymes. METHODS: The different (immunoinhibition, electrophoretic, immunochemistry) assays for determination of a cardiac marker (creatine kinase 2) are compared in hospital patients. Isoform analysis of alkaline phosphatase is performed in benign, transient hyperphosphatasemia. RESULTS: The author reviews recent knowledge on polymorphism of creatine kinase (isoenzymes, isoforms, macro types), and alkaline phosphatase (isoenzymes, their cancer related variants, isoforms). The origin of falsely high cardiac marker (creatine kinase 2) determined by the immunoinhibition assay could be related to the presence of macro creatine kinase (both types), creatine kinase isoenzyme 1, and their mixtures. After reviewing the recent findings on the syndrome of benign, transient hyperphosphatasemia, a case of a 1-year-old Hungarian boy with this syndrome is presented. CONCLUSIONS: The author points out that the appropriate use of clinical proteomics (the polymorphisms of creatine kinase and alkaline phosphatase enzymes) may improve the diagnostic efficiency of the clinical laboratory tests.

Alkaline Phosphatase↗
PubMed2005

TRPMs and neuronal cell death.

Death of CNS neurons during acute injury occurs as a result of a complex combination of excitotoxicity, necrosis, apoptosis, oedema and inflammatory reactions. Neuroprotection via glutamate receptor blockade or antioxidant or anti-inflammatory therapy have not proven effective in the clinical treatment of brain damage due to narrow therapeutic windows, poor pharmacokinetics or blockade of the signalling essential for normal excitatory neurotransmission and neuronal survival. Recent work in neuronal biochemistry, genomics and proteomics has increased understanding of the molecular organization of the excitatory synapse and the neuronal postsynaptic density. Transient receptor potential (TRP) channels are an exciting new family of cation channels that are highly expressed in the brain. Several members can be induced by oxidative stress and oxygen free radicals, both of which play important roles in neurodegeneration. Recent work has indicated that members of the melastatin subfamily (TRPM) of TRP proteins, particularly TRPM7 and TRPM2, may play key roles in neuronal death that is activated by oxidative stress and downstream from excitotoxic signal pathways. This discovery provides an exiting new avenue for research into the pathophysiology and treatment of acute neurodegeneration.

Calcium↗
PubMed2003

Deranged hypothetical proteins Rik protein, Nit protein 2 and mitochondrial inner membrane protein, Mitofilin, in fetal Down syndrome brain.

Down syndrome (DS) is the most common genetic disorder with mental retardation and a host of deranged proteins has already been described. Protein hunting leads to rapid accumulation of aberrant proteins and proteomics methods not only allow unambiguous identification of proteins, they are also a powerful tools to identify new or predicted proteins. We applied two-dimensional gel electrophoresis with in-gel digestion of proteins and subsequent MALDI-TOF mass-spectrometrical identification and quantification of spots using specific software on cortical brain samples from 7 controls and 7 samples from fetal DS at the early second trimester. Nine hypothetical proteins were identified: three of them (4833418L03Rik protein Q9D614, mitochondrial inner membrane protein Q16891 and Nit protein 2 Q8WUF0) were significantly and about doublefold reduced in fetal DS brain. Hypothetical proteins CGI 99, FLJ10463, 70 kDa WD-repeat tumor rejection antigen homolog, KSRP, Hypothetical protein 49.6 kDa and Elongin A were comparable between groups. Domain analysis of deranged structures revealed a t_SNARE domain for the Rik protein, indicating involvement of this protein in the exocytotic-synaptic machinery impaired in DS, a CN hydrolase domain for Nit protein 2, possibly reflecting aberrant nitrilase-related metabolism and handling and an inner mitochondrial protein, extending knowledge on the mitochondrial deficit in in fetal DS early in life.

Aborted Fetus↗
PubMed2006

Decreased levels of apolipoprotein A-I in plasma of schizophrenic patients.

This study aims to identify the effects of antipsychotics on plasma proteins, and on the proteins associated with schizophrenia. We applied proteomics technology to screen protein aberrations in Sprague-Dawley rats treated with antipsychotics and schizophrenic patients undergoing medication. ApoA-I was found significantly increased in the chlorpromazine-treated rats and decreased in the patients with treatment-resistant schizophrenia, which suggest that decreased levels of apoA-I might be associated with the pathology of schizophrenia and that chlorpromazine increases apoA-I levels as part of its therapeutic action.

Adult↗
PubMed2004

Comprehensive proteome expression profiling of undifferentiated versus differentiated neural stem cells from adult rat hippocampus.

Adult neural stem cells can be isolated from various regions of the rat brain and seem to have multilineage differentiation potential. In this study, we investigated the hypothesis that global protein expression of adult neural stem cells isolated from rat hippocampus is changed during in vitro differentiation. After 2 days of differentiation, we separated total protein extracts by two-dimensional gel electrophoresis and used mass spectrometry and gel-matching for identification. We detected a differential expression in 367 regulated protein spots, of which 128 could be identified. Regulated proteins included participants in transcription and DNA metabolism; signal transduction and Ca2+-signaling; MAP kinase pathways; cytoskeletal rearrangement; regulation of cell cycle, proliferation, and survival; protein biosynthesis, folding, and degradation; and glycine and glutamate metabolic pathways. These results suggest a massive reorganization of the stem cell proteomic profile upon differentiation and indicate potential cellular targets mediating the differentiation of neural stem cells.

Animals↗
PubMed2026

Freezing with Light: Photo-Cross-Linking-Assisted Platform Enables GPCR Deorphanization.

Despite their success as drug targets, nearly one hundred G protein-coupled receptors (GPCRs) remain orphan without identified endogenous ligands. Defining these ligand-receptor pairs constitute a fundamental prerequisite for understanding receptor biology and rational drug discovery. However, deorphanization remains inherently challenging due to the transient and interface-specific ligand-GPCR interactions, especially for endogenous ones that are embedded within chemically complex environments. This In Focus article highlights a modularly designed platform that integrates site-specific photo-cross-linking reaction with proteomics to enable ligand-GPCR pairing directly in native biological contexts. Using this strategy, neuropeptide L-LEN was identified as the endogenous ligand for GPR50, forming a regulatory axis that controls energy expenditure and thermogenesis through brain-peripheral interactions.

Receptors, G-Protein-Coupled↗
PubMed2004

Mitochondrial building blocks.

Despite many genomic and proteomic attempts, approximately half of all mitochondrial proteins remain unidentified. Moreover, the composition of mitochondria varies in different mammalian cell types and the details of this tissue specificity are unclear. Two recent reports provide a major advance in our understanding of mitochondrial function. Sickmann et al. used an exhaustive proteomic approach and came very close to identifying the complete set of yeast mitochondrial proteins. Mootha et al. examined mitochondria from mouse brain, heart, kidney and liver cells, finding that a surprising fraction of the proteins are expressed in only a subset of tissues.

Animals↗
PubMed2006

Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum.

The postsynaptic density (PSD) of central excitatory synapses is essential for postsynaptic signaling, and its components are heterogeneous among different neuronal subtypes and brain structures. Here we report large scale relative and absolute quantification of proteins in PSDs purified from adult rat forebrain and cerebellum. PSD protein profiles were determined using the cleavable ICAT strategy and LC-MS/MS. A total of 296 proteins were identified and quantified with 43 proteins exhibiting statistically significant abundance change between forebrain and cerebellum, indicating marked molecular heterogeneity of PSDs between different brain regions. Moreover we utilized absolute quantification strategy, in which synthetic isotope-labeled peptides were used as internal standards, to measure the molar abundance of 32 key PSD proteins in forebrain and cerebellum. These data confirm the abundance of calcium/calmodulin-dependent protein kinase II and PSD-95 and reveal unexpected stoichiometric ratios between glutamate receptors, scaffold proteins, and signaling molecules in the PSD. Our data also demonstrate that the absolute quantification method is well suited for targeted quantitative proteomic analysis. Overall this study delineates a crucial molecular difference between forebrain and cerebellar PSDs and provides a quantitative framework for measuring the molecular stoichiometry of the PSD.

Animals↗
PubMed2026

A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.

Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities with adult glioma, it comprises distinct disease entities. In this study, we longitudinally profile a molecularly diverse cohort of 16 pHGG patients through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of neoplastic and microenvironmental features during disease progression and treatment. We define a set of core pHGG neoplastic cell states and observe differential tumor-myeloid interactions between malignant cell phenotypes. We find that essential neuromodulators and the interferon response are upregulated post-therapy, implicating them as malignant cell-intrinsic targets. We observe an increase in oligodendrocytes upon progression and that they coordinate spatial motifs with proneural tumor cells. This multiomic atlas of longitudinal pHGG captures features of therapy response and provides a scalable reference for the study of pediatric brain tumors.

Humans↗
PubMed2006

Proteomic analysis of mice hippocampus in simulated microgravity environment.

Space travel induces many deleterious effects on the flight crew due to the '0' g environment. The brain experiences a tremendous fluid shift, which is responsible for many of the detrimental changes in physical behavior seen in astronauts. It therefore indicates that the brain may undergo major changes in its protein levels in a '0' g environment to counteract the stress. Analysis of these global changes in proteins may explain to better understand the functioning of brain in a '0' g condition. Toward such an effort, we have screened proteins in the hippocampus of mice kept in simulated microgravity environment for 7 days and have observed a few changes in major proteins as compared to control mice. Essentially, the results show a major loss of proteins in the hippocampus of mice subjected to simulated microgravity. These changes occur in structural proteins such as tubulin, coupled with the loss of proteins involved in metabolism. This preliminary investigation leads to an understanding of the alteration of proteins in the hippocampus in response to the microgravity environment.

Animals↗
PubMed2026

A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes.

Stem-cell-based in vitro models offer promising potential to elucidate human brain cell functions and interactions, but limitations in reproducibility, maturation and cell-type diversity persist. Especially, prolonged incorporation of mature microglia and studies of neuroinflammation have proven challenging. Here, we developed a human induced pluripotent stem cell-based three-dimensional cortical brain tissue model (3BTM) containing neurons, astrocytes and microglia with high reproducibility, maturity and viability. 3BTMs show morphological, functional and proteomic maturation of all cell types, leading to high similarity to their in vivo counterparts. Incorporated microglia survive for over 6 months and display mature morphology, functions and gene expression. Importantly, when engineered to model Alzheimer's disease pathology, 3BTMs recapitulate key disease hallmarks, including amyloid deposition, increased phospho-tau levels and neuroinflammation, with microglia shifting their transcriptional landscape to disease-relevant signatures. Treatment of Alzheimer's disease 3BTMs with anti-Aβ immunotherapy cleared deposits and largely reversed disease signatures in glia. Together, our microglia-containing model provides a platform for studying physiological and pathological states of human brain tissue.

Humans↗
PubMed2026

Proteins as Regulators of Metabolic Changes in Sepsis: Alterations in Body Fluids, Immune Cells, and Organs through the Eyes of Proteomics.

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection and profound metabolic alterations that contribute to immune dysfunction and organ failure. This Review synthesizes proteomic evidence on sepsis-associated alterations in proteins involved in metabolic pathways across circulating biofluids, immune cells, and organs. Across plasma and urine, proteomic studies identify disturbances in lipoprotein-associated pathways, redox homeostasis, mitochondrial function, and substrate metabolism, indicating that protein signatures of metabolic dysregulation are systemic and detectable across biofluids. In immune cells, monocytes and neutrophils, proteomic analyses reveal a shift toward glycolysis with concurrent impairment of mitochondrial pathways alongside phenotype-dependent differences in lipid and redox-related programs. Organ-level studies further show that metabolic responses are heterogeneous, with distinct trajectories in the kidney, heart, liver, lung, skeletal muscle, and brain. These observations support the concept that sepsis involves compartment-specific remodeling of metabolism-associated protein networks rather than a single convergent metabolic state. Proteomics also highlights potential translational opportunities by identifying metabolism-associated proteins linked to disease severity, clinical phenotypes, and biologically distinct patient subgroups, although the current evidence remains largely exploratory and context-dependent. Overall, proteomics provides a complementary framework for understanding the molecular regulation of sepsis-associated metabolic dysfunction and may refine biological stratification and therapeutic targeting, particularly when integrated with longitudinal sampling and multiomic data.

Humans↗
PubMedDate not supplied

Elevated levels of alpha-2-Heremans-Schmid glycoprotein in CSF of patients with low-grade gliomas.

Little is known about the expression of mitogens and other tumour-related substances in the cerebrospinal fluid (CSF) of glioma patients. The aim of the current study was to determine the presence of aberrant proteins in the CSF of patients with low-grade gliomas. Lumbar puncture was performed in 8 adult patients with supratentorial low-grade gliomas at the time of diagnosis and in 7 controls. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation time of flight mass spectrometry were used to detect and quantify deviant proteins in the CSF. Two isoforms of alpha(2)-Heremans-Schmid glycoprotein (AHSG) were identified and demonstrated in higher levels in patients with low-grade gliomas compared with the control group consisting of patients with mixed neurological diagnoses (p = 0.001 and p = 0.04, respectively). In 1 patient, the level of AHSG was significantly reduced after gross total resection of the tumour. AHSG appears in the present proteome screening as a novel substance in glioma research. This glycoprotein is expressed in the fetal human brain and is believed to be involved in the embryonic development of the neocortex. Further analyses are planned to determine the significance of the increased levels of AHSG in the CSF of patients with low-grade gliomas.

Adult↗
PubMed2025

Protective effects of liver-derived apolipoprotein A1 against heat stress-induced hypothalamic lipid metabolism and blood-brain barrier integrity.

Heat stress (HS), a prevalent occupational and environmental hazard, has increasingly been recognized as a major contributor to multiple physiological disorders. The hypothalamus, a key regulator of thermoregulation and endocrine signaling, is especially susceptible to metabolic and inflammatory disturbances induced by HS. This study investigates the interplay among lipid metabolism, blood-brain barrier (BBB) integrity, and neuroinflammation in the hypothalamus under HS conditions, with a specific focus on apolipoprotein A1 (APOA1) as a potential protective factor. To achieve this, we integrated proteomic and lipidomic analyses with experimental validation in porcine and murine models. Proteomic analysis identified 266 differentially expressed proteins (DEPs) in the hypothalamus following HS, with significant enrichment in lipid metabolism pathways-especially glycerophospholipid (GP) metabolism-in which APOA1 displayed a marked increase. Lipidomic profiling further revealed HS-induced disruptions in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) metabolism. Additionally, blood-brain barrier integrity was compromised, as evidenced by increased perivascular IgG extravasation, reduced pericyte coverage, and decreased expression of tight junction proteins ZO-1 and Occludin. HS also triggered pronounced neuroinflammation, characterized by elevated levels of iNOS, GFAP, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Notably, administration of D-4F, an APOA1 mimetic peptide, alleviated blood-brain barrier damage, reduced neuroinflammation, and preserved synaptic integrity, thereby suggesting a neuroprotective role for APOA1 in HS-induced hypothalamic dysfunction. These findings underscore the critical role of lipid metabolism in maintaining hypothalamic homeostasis under HS conditions and position APOA1 as a key regulator with potential therapeutic implications for mitigating HS-related neuroinflammatory and metabolic disturbances.

Blood-Brain Barrier↗
PubMedDate not supplied

Genotypes and phenotypes.

Within the framework of a pilot project on the analysis of the mouse proteome, we investigated C57BL/6 mice (Mus musculus), a standard inbred strain of the mouse, starting with the analysis of brain, liver and heart proteins. Tissue extraction and the separation of proteins were performed with techniques offering a maximum of resolution. Proteins separated were analyzed by mass spectrometry. Gene-protein identification was performed by genetic analyses using the European Collaborative Interspecific Backcross (EUCIB), established from the two mouse species Mus musculus and Mus spretus. On the basis of protein polymorphisms we mapped hundreds of genes on the mouse chromosomes, allowing us new insight into the relationship between genotype and phenotype of proteins. In particular, the results showed that protein modifications can be genetically determined, therefore representing their own class of protein phenotypes. In this context, results are discussed suggesting that phenotypes of single protein species may result from several genes. Accordingly, proteins are considered as polygenic traits. In contrast, one example demonstrates that proteins may also have pleiotropic effects: a single gene mutation (a single altered protein) may affect several other proteins. From these studies we conclude that gene-related functional proteomics will show in the future that genetic diseases, defined today by clinical symptoms and considered as etiological entireties, can be subdivided into different diseases according to different affected genes.

Animals↗