A5048115842- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- Cholinesterase and Neurodegenerative Diseases
- Cancer Genomics and Diagnostics
- Neurobiology and Insect Physiology Research
- Bioinformatics and Genomic Networks
- Receptor Mechanisms and Signaling
- Genetics, Bioinformatics, and Biomedical Research
- Advanced Proteomics Techniques and Applications
- Biomedical and Engineering Education
- S100 Proteins and Annexins
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- Ferroptosis and cancer prognosis
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Intracerebral and Subarachnoid Hemorrhage Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Mass Spectrometry Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Biotin and Related Studies
- Biotechnology and Related Fields
- Protease and Inhibitor Mechanisms
- Lipid Membrane Structure and Behavior
The Hyve (Netherlands)
2020-2025
Vrije Universiteit Amsterdam
2003-2022
Dana-Farber Cancer Institute
2022
Amsterdam UMC Location Vrije Universiteit Amsterdam
2018-2022
Amsterdam Neuroscience
2009-2022
Max Delbrück Center
2012
Babraham Institute
2012
Merck & Co., Inc., Rahway, NJ, USA (United States)
2005
Pfizer (United States)
2005
The Research Network
2005
Abstract International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international registry collecting from 19 centers, makes >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional longitudinal data, including treatment outcome are being collected by GENIE Biopharma Collaborative using PRISSMM curation...
Abstract Introduction We performed a comprehensive quantitative proteomics study on human hippocampus tissue involving all Braak stages to assess changes in protein abundance over the various of Alzheimer's disease (AD). Methods Hippocampal subareas CA1 and subiculum 40 cases were isolated using laser capture microdissection analyzed mass spectrometry. Immunoblotting immunohistochemistry used for validation. Results Over stages, an altered expression was found 372 proteins including levels...
Alzheimer's disease is caused by increased production or reduced clearance of amyloid-β, which results in the formation amyloid-β plaques and triggers a cascade downstream events leading to progressive neurodegeneration. The earliest clinical symptoms disease, i.e., memory loss, are however poorly understood from molecular cellular perspective. Here we used APPswe/PS1dE9 (APP/PS1) transgenic mice study early pre-pathological effects levels on hippocampal synaptic plasticity memory. Using an...
Alterations in the hippocampal extracellular matrix contribute to cognitive deficits rats exhibiting a chronic depressive-like state after exposure social defeat–induced persistent stress.
Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) deposits as plaques in the parenchyma and walls of cortical leptomeningeal blood vessels brain called cerebral angiopathy (CAA). It suggested that CAA type-1, which refers to deposition both capillaries larger vessels, adds symptomatic manifestation AD correlates with severity. Currently, cannot be diagnosed pre-mortem mechanisms involved are elusive. To obtain insight mechanism identify marker proteins specifically associated we...
Development of the brain involves formation and maturation numerous synapses. This process requires prominent changes synaptic proteome potentially thousands different proteins at every synapse. To date analysis synapse development has been studied sparsely. Here, we analyzed cortical membrane juvenile postnatal days 9 (P9), P15, P21, P27, adolescent (P35) adult ages P70, P140 P280 C57Bl6/J mice. Using a quantitative proteomics workflow quantified 1560 which 696 showed statistically...
Alzheimer’s disease is caused by increased production or reduced clearance of amyloid-β, which results in the formation amyloid-β plaques and triggers a cascade downstream events leading to progressive neurodegeneration. The earliest clinical symptoms disease, i.e., memory loss, are however poorly understood from molecular cellular perspective. Here we used APPswe/PS1dE9 (APP/PS1) transgenic mice study early pre-pathological effects levels on hippocampal synaptic plasticity memory. Using an...
We report here that unlike what was suggested for many vertebrate neurons, synaptic transmission in <i>Lymnaea stagnalis</i> occurs independent of a physical interaction between presynaptic calcium channels and functional complement SNARE proteins. Instead, <i>Lymnaea</i>requires the expression C-terminal splice variant the<i>Lymnaea</i> homolog to mammalian N- P/Q-type channels. show alternately spliced region physically interacts with scaffolding proteins Mint1 CASK, is abolished following...
The freshwater snail Lymnaea stagnalis (L. stagnalis) has served as a successful model for studies in the field of Neuroscience. However, serious drawback molecular analysis nervous system L. been lack large-scale genomic or neuronal transcriptome information, thereby limiting use this unique model.In study, we report 7,712 distinct EST sequences (median length: 847 nucleotides) normalized central (CNS) cDNA library, resulting largest collection data currently available. Approximately 42%...
Optimization of fragment hits toward high-affinity lead compounds is a crucial aspect fragment-based drug discovery (FBDD). In the current study, we have successfully optimized by growing into ligand-inducible subpocket binding site acetylcholine-binding protein (AChBP). This soluble homologue ligand domain (LBD) Cys-loop receptors. The optimization was monitored with X-ray structures complexes and systematic thermodynamic analyses using surface plasmon resonance (SPR) biosensor analysis...
Age-related cognitive decline is a serious health concern in our aging society. Decreased function observed during healthy brain most likely caused by changes connectivity and synaptic dysfunction particular regions. Here we show that aged C57BL/6J wild-type mice have hippocampus-dependent spatial memory impairments. To identify the molecular mechanisms are relevant to these deficits, investigated temporal profile of mouse hippocampal proteome at 20, 40, 50, 60, 70, 80, 90, 100 weeks age....
Aging is the most important risk factor for neurodegenerative diseases associated with pathological protein aggregation such as Alzheimer's disease. Although aging an player, it remains unknown which molecular changes are relevant disease initiation. Recently has become apparent that widespread a common feature of aging. Indeed, several studies demonstrate hundreds proteins highly insoluble age, in absence obvious processes. Yet unclear how these misfolded aggregating age affect diseases....
Frontotemporal dementia is characterized by progressive atrophy of frontal and/or temporal cortices at an early age onset. The disorder shows considerable clinical, pathological, and genetic heterogeneity. Here we investigated the proteomic signatures cortex from brains with frontotemporal due to GRN MAPT mutations identify key cell types molecular pathways in their pathophysiology. We compared patients gene (n = 9) or 13) non-demented controls 11). Using quantitative analysis on...
During brain development, the neocortex shows periods of enhanced plasticity, which enables acquisition knowledge and skills that we use build on in adult life. Key to persistent modifications neuronal connectivity plasticity are molecular changes occurring at synapse. Here used isobaric tag for relative absolute quantification measure levels 467 synaptic proteins a well-established model mouse visual cortex regulation its critical period. We found inducing by monocular deprivation during...
We created SynSysNet, available online at http://bioinformatics.charite.de/synsysnet, to provide a platform that creates comprehensive 4D network of synaptic interactions. Neuronal synapses are fundamental structures linking nerve cells in the brain and they responsible for neuronal communication information processing. These processes dynamically regulated by proteins. New developments interaction proteomics yeast two-hybrid methods allow unbiased detection interactors. The consolidation...
Acetylcholine (ACh) is a neurotransmitter commonly found in all animal species. It was shown to mediate fast excitatory and inhibitory neurotransmission the molluscan CNS. Since early intracellular recordings, it that receptors mediating these currents belong family of neuronal nicotinic acetylcholine they can be distinguished on basis their pharmacology. We previously identified 12 Lymnaea cDNAs were predicted encode ion channel subunits receptors. These nAChRs subdivided groups according...
We described a family of nicotinic acetylcholine receptor (nAChR) subunits underlying cholinergic transmission in the central nervous system (CNS) mollusc Lymnaea stagnalis. By using degenerate PCR cloning, we identified 12 that display high sequence similarity to nAChR subunits, which 10 are alpha-type, 1 is beta-type, and was not classified because insufficient information. Heterologous expression confirms their capacity form functional receptors responding acetylcholine. The alpha-type...
Astrocytes are being increasingly recognized as crucial contributors to neuronal function at synapses, axons, and somas. Reliable methods that can provide insight into astrocyte proteins the neuron-astrocyte functional interface highly desirable. Here, we conducted a mass spectrometry analysis of Percoll gradient-isolated gliosomes, viable preparation glial subcellular particles often used study mechanisms astrocytic transmitter uptake release their regulation. Gliosomes were compared with...
Abstract cBioPortal for Cancer Genomics is a widely used platform exploratory, interactive visualization and analysis of large-scale clinico-genomic datasets. provides range visualizations analyses including cohort exploration, OncoPrints, mutation “lollipop” plots, survival analysis, alteration enrichment detailed patient-level visualizations. also integrates variant annotations from variety sources to facilitate interpretation. The public (https://www.cbioportal.org) accessed by...
Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two isoforms, β- and γ-actin, are expressed in dendritic spines, specific contribution γ-actin expression synaptic is unknown. We show that levels regulated by E3 ubiquitin ligase TRIM3. TRIM3 protein Actg1 transcript colocalized messenger ribonucleoprotein granules responsible for targeting RNAs. polyubiquitylates most likely cotranslationally at sites. Trim3−/− mice consequently have increased hippocampal synapses,...
Cognitive decline is one of the earliest hallmarks both normal and pathological brain aging. Here we used Ercc1 mutant mice, which are impaired in multiple DNA repair systems consequently show accelerated aging progressive memory deficits, to identify changes levels hippocampal synaptic proteins that potentially underlie these age-dependent deficits. Aged mice gross dendritic morphology synapse numbers, neurons displayed outgrowth formation vitro. However, using isobaric tag for relative...
A change in efficacy of hippocampal synapses is critical for memory formation. So far, the molecular analysis during learning has focused on small groups proteins, whereas dynamic global changes at these have remained unknown. Here, we analyzed temporal mouse synaptic membrane proteome 1 and 4 h after contextual fear learning, comparing two groups; (1) a forming "delayed-shock" group (2) memory-deficient "immediate-shock" group. No protein expression were observed conditioning between...