299 results match your criteria: "VIB Center for the Biology of Disease[Affiliation]"

Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain.

Life Sci Alliance

July 2023

European Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

In age-related neurodegenerative diseases, like Alzheimer's and Parkinson's, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm and human cell models for diseases. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown.

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Choroid plexus-derived extracellular vesicles exhibit brain targeting characteristics.

Biomaterials

November 2022

VIB Center for Inflammation Research, VIB, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium. Electronic address:

The brain is protected against invading organisms and other unwanted substances by tightly regulated barriers. However, these central nervous system (CNS) barriers impede the delivery of drugs into the brain via the blood circulation and are therefore considered major hurdles in the treatment of neurological disorders. Consequently, there is a high need for efficient delivery systems that are able to cross these strict barriers.

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Ongoing neural activity has been observed across several brain regions and is thought to reflect the internal state of the brain. Yet, it is important to understand how ongoing neural activity interacts with sensory experience and shapes sensory representations. Here, we show that the projection neurons of the fruit fly antennal lobe exhibit spatiotemporally organized ongoing activity.

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Synapses are critical for neuronal communication and brain function. To maintain neuronal homeostasis, synapses rely on autophagy. Autophagic alterations cause neurodegeneration and synaptic dysfunction is a feature in neurodegenerative diseases.

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Increasing evidence indicates that extracellular vesicles (EVs) play an important role in the pathogenesis of Alzheimer's disease (AD). We previously reported that the blood-cerebrospinal fluid (CSF) interface, formed by the choroid plexus epithelial (CPE) cells, releases an increased amount of EVs into the CSF in response to peripheral inflammation. Here, we studied the importance of CP-mediated EV release in AD pathogenesis.

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The physical distance between presynaptic Ca channels and the Ca sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). While STP is highly diversified across synapse types, the computational and behavioral relevance of this diversity remains unclear. In the Drosophila brain, at nanoscale level, we can distinguish distinct coupling distances between Ca channels and the (m)unc13 family priming factors, Unc13A and Unc13B.

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The two faces of synaptic failure in App knock-in mice.

Alzheimers Res Ther

August 2020

Brain and Cognition, KU Leuven, Tiensestraat 102, Box 3714, 3000, Leuven, Belgium.

Background: Intensive basic and preclinical research into Alzheimer's disease (AD) has yielded important new findings, but they could not yet been translated into effective therapies. One of the reasons is the lack of animal models that sufficiently reproduce the complexity of human AD and the response of human brain circuits to novel treatment approaches. As a step in overcoming these limitations, new App knock-in models have been developed that avoid transgenic APP overexpression and its associated side effects.

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The Mystery of Rap1 Suppression of Oncogenic Ras.

Trends Cancer

May 2020

VIB Center for the Biology of Disease and KU Leuven Department of Oncology, Leuven Cancer Institute, Leuven, Belgium.

Decades ago, Rap1, a small GTPase very similar to Ras, was observed to suppress oncogenic Ras phenotype, reverting its transformation. The proposed reason, persisting since, has been competition between Ras and Rap1 for a common target. Yet, none was found.

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A neurodevelopmental origin of behavioral individuality in the visual system.

Science

March 2020

Institut du Cerveau et de la Moelle Epinière (ICM)-Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.

The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using , we demonstrate a link between stochastic variation in brain wiring and behavioral individuality.

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Antigen receptor-dependent (AgR-dependent) stimulation of the NF-κB transcription factor in lymphocytes is a required event during adaptive immune response, but dysregulated activation of this signaling pathway can lead to lymphoma. AgR stimulation promotes assembly of the CARMA1-BCL10-MALT1 complex, wherein MALT1 acts as (a) a scaffold to recruit components of the canonical NF-κB machinery and (b) a protease to cleave and inactivate specific substrates, including negative regulators of NF-κB. In multiple lymphoma subtypes, malignant B cells hijack AgR signaling pathways to promote their own growth and survival, and inhibiting MALT1 reduces the viability and growth of these tumors.

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The long noncoding RNA regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43.

Sci Adv

December 2019

Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, Excellence Cluster Multiscale Bioimaging, 37073 Göttingen, Germany.

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified , a neuron-specific nuclear lncRNA conserved from rodents to humans.

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Genetically engineered mouse lines on a C57BL/6J background are widely employed as preclinical models to study neurodegenerative human disorders and brain tumors. However, because of the lack of comprehensive data on the spontaneous background neuropathology of the C57BL/6J strain, discriminating between naturally occurring changes and lesions caused by experimental mutations can be challenging. In this context, this study aims at defining the spectrum and frequency of spontaneous brain changes in a large cohort of C57BL/6J mice and their association with specific biological variables, including age and sex.

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Targeted editing of the PSIP1 gene encoding LEDGF/p75 protects cells against HIV infection.

Sci Rep

February 2019

Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000, Leuven, Belgium.

To fulfill a productive infection cycle the human immunodeficiency virus (HIV) relies on host-cell factors. Interference with these co-factors holds great promise in protecting cells against HIV infection. LEDGF/p75, encoded by the PSIP1 gene, is used by the integrase (IN) protein in the pre-integration complex of HIV to bind host-cell chromatin facilitating proviral integration.

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Glycine receptors (GlyRs) containing the α2 subunit are highly expressed in the developing brain, where they regulate neuronal migration and maturation, promote spontaneous network activity and subsequent development of synaptic connections. Mutations in are associated with autism spectrum disorder, but the underlying pathophysiology is not described yet. Here, using -knockout mice, we found a GlyR-dependent effect on neonatal spontaneous activity of dorsal striatum medium spiny neurons (MSNs) and maturation of the incoming glutamatergic innervation.

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Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health. Drosophila melanogaster is a powerful model to study small-scale, temporally-transient social behavior.

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Spontaneous pulmonary co-metastasis of hepatoblastoma arising within a hepatocellular carcinoma in an aged C57BL/6J mouse.

J Toxicol Pathol

July 2018

Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA 19104-6051, U.S.A.

Murine hepatoblastoma (HB) is a rare spontaneous tumor with controversial histogenesis. It mainly occurs in aged males, frequently in close association with preexisting hepatocellular neoplasms. The present work describes a spontaneous HB arising within a hepatocellular carcinoma (HCC) in a 22-month-old male C57BL/6J mouse.

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Microbial communities as dynamical systems.

Curr Opin Microbiol

August 2018

Department of Microbiology and Immunology, Rega institute, Herestraat 49, KU Leuven, 3000 Leuven, Belgium. Electronic address:

Nowadays, microbial communities are frequently monitored over long periods of time and the interactions between their members are explored in vitro. This development has opened the way to apply mathematical models to characterize community structure and dynamics, to predict responses to perturbations and to explore general dynamical properties such as stability, alternative stable states and periodicity. Here, we highlight the role of dynamical systems theory in the exploration of microbial communities, with a special emphasis on the generalized Lotka-Volterra (gLV) equations.

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Introduction: Tauopathies are neurodegenerative diseases characterized by TAU protein-related pathology, including frontotemporal dementia and Alzheimer's disease among others. Mutant TAU animal models are available, but none of them faithfully recapitulates human pathology and are not suitable for drug screening.

Methods: To create a new in vitro tauopathy model, we generated a footprint-free triple MAPT-mutant human induced pluripotent stem cell line (N279K, P301L, and E10+16 mutations) using clustered regularly interspaced short palindromic repeats-FokI and piggyBac transposase technology.

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Background: Growth rates, interactions between community members, stochasticity, and immigration are important drivers of microbial community dynamics. In sequencing data analysis, such as network construction and community model parameterization, we make implicit assumptions about the nature of these drivers and thereby restrict model outcome. Despite apparent risk of methodological bias, the validity of the assumptions is rarely tested, as comprehensive procedures are lacking.

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Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. Whereas conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors. Here, we found that pDCs developed predominantly from IL-7R lymphoid progenitor cells.

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Activation of the maternal immune system during pregnancy is a well-established risk factor for neuropsychiatric disease in the offspring, yet, the underlying mechanisms leading to altered brain function remain largely undefined. Microglia, the resident immune cells of the brain, are key to adequate development of the central nervous system (CNS), and are prime candidates to mediate maternal immune activation (MIA)-induced brain abnormalities. As such, the effects of MIA on the immunological phenotype of microglia has been widely investigated.

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A Temporal Transcriptional Switch Governs Stem Cell Division, Neuronal Numbers, and Maintenance of Differentiation.

Dev Cell

April 2018

Institut du Cerveau et de la Moelle Epinière (ICM) - Hôpital Pitié-Salpêtrière, Sorbonne Université, Inserm, CNRS, Paris, France; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium. Electronic address:

The importance of producing the correct numbers of neurons during development is illustrated by both evolutionary enhancement of cognitive capacities in larger brains, and developmental disorders of brain size. In humans, increased neuronal numbers during development is speculated to partly derive from a unique subtype of neural stem cells (NSCs) that undergo a phase of expansion through symmetric self-amplifying divisions before generating neurons. Symmetric amplification also appears to underlie adult neural stem maintenance in the mouse.

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Very little to no improvement in overall survival has been seen in patients with advanced non-resectable cutaneous melanoma or metastatic uveal melanoma in decades, highlighting the need for novel therapeutic options. In this study we investigated as a potential novel therapeutic intervention for both cutaneous and uveal melanoma patients a combination of the broad spectrum HDAC inhibitor quisinostat and pan-CDK inhibitor flavopiridol. Both drugs are currently in clinical trials reducing time from bench to bedside.

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Adult mammalian central nervous system (CNS) neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury.

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