A5001925807- Alzheimer's disease research and treatments
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Extracellular vesicles in disease
- Neuroscience and Neural Engineering
- Drug Transport and Resistance Mechanisms
- Mitochondrial Function and Pathology
- Viral Infectious Diseases and Gene Expression in Insects
- Nerve injury and regeneration
- CAR-T cell therapy research
- Prion Diseases and Protein Misfolding
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- Cancer therapeutics and mechanisms
- Advanced Biosensing Techniques and Applications
- Cholinesterase and Neurodegenerative Diseases
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Conducting polymers and applications
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- Cellular transport and secretion
Université de Lille
2016-2025
Inserm
2016-2025
Centre Hospitalier Universitaire de Lille
2010-2024
Lille Neurosciences & Cognition
2019-2024
Centre de Recherche Jean Pierre Aubert
2013-2023
Centre National de la Recherche Scientifique
2017-2022
Université Paris-Saclay
2017
MaineGeneral Medical Center
2017
Harvard University
2017
Massachusetts General Hospital
2017
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described microtubule-associated protein, has also been observed the nuclei of and non-neuronal cells. However, function nuclear form Tau neurons not yet elucidated. In this work, we demonstrate that acute oxidative stress mild heat (HS) induce accumulation dephosphorylated nuclei. Using chromatin immunoprecipitation assays, capacity endogenous to interact with DNA increased...
A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer are found various types, including neurons. We show the microtubule-associated protein Tau, key player Alzheimer's disease, is bona fide constituent TNTs. This important because Tau...
In sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. human brain, hierarchical pathways this neurodegeneration have been well established in Alzheimer’s disease (AD) and other tauopathies such as argyrophilic grain disorder progressive supranuclear palsy but molecular cellular mechanisms supporting progression are yet not known. These appear to be associated with intercellular transmission pathology, recently...
Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested may be secreted and play role neural network signalling. However, once deregulated, also participate the spreading of pathology hierarchical pathways neurodegeneration. The mechanisms underlying neuron-to-neuron transfer are still unknown; given extra-cellular vesicles cell-to-cell communication, we wondered whether these could carry Tau. We found,...
Tauopathies are neurodegenerative diseases characterized by the intraneuronal accumulation of aggregated tau. The staging this process is well established for Alzheimer's disease as other tauopathies. stereotypical pattern tau pathology in these consistent with hypothesis that protein can spread a 'prion-like' manner. It proposes extracellular pathological species transmit from cell to cell. Accordingly, targeting spreading therapeutic antibodies one should be able slow or halt progression...
Abstract Pericentromeric heterochromatin (PCH) gives rise to highly dense chromatin sub-structures rich in the epigenetic mark corresponding trimethylated form of lysine 9 histone H3 (H3K9me3) and protein 1α (HP1α), which regulate genome expression stability. We demonstrate that Tau, a involved number neurodegenerative diseases including Alzheimer’s disease (AD), binds localizes within or next neuronal PCH primary cultures from wild-type mice. Concomitantly, we show clustered distribution...
Tauopathies are a heterogeneous group of pathologies characterized by tau aggregation inside neurons. Most them sporadic but certain tauopathies rely on gene (MAPT) mutations. They particularly differ from one to another their different neuropathological signatures e.g. lesion shapes, regions affected and molecular composition aggregates. Six isoforms exist, they do not all co-aggregate in each tauopathy rather have unique signature for one. In some such as Alzheimer's disease (AD), protein...
Tau proteins aggregate into filaments in brain cells Alzheimer's disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting immuno-modulators its pathologic seeding. A VHH issued from the screen against a synthetic phage-display library humanized VHHs was selected for capacity bind microtubule-binding domain, composing core fibrils. This parent optimized improve biochemical...
Our aims are to review animal models of tauopathies, which include a number brain disorders with various aetiologies, including ageing, genetics, infectious diseases, toxins, trauma and other unknown factors. Tauopathies characterized by the accumulation filaments microtubule‐associated tau protein. The different aetiopathogeneses distinct molecular events involved in aggregation have led development for these diseases. In this review, rather than listing all current models, we focus on...
Although the brain accounts for only 2% of total body mass, it consumes most energy. Neuronal metabolism is tightly controlled, but remains poorly understood how neurons meet their energy demands to sustain synaptic transmission. Here we provide evidence that AMP-activated protein kinase (AMPK) pivotal neuronal levels upon activation by adapting rate glycolysis and mitochondrial respiration. Furthermore, this metabolic plasticity required expression immediate-early genes, plasticity, memory...
Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by synaptic loss that leads to the development of cognitive deficits. Synapses are neuronal structures play crucial role in memory formation and known consume most energy used brain. Interestingly, AMP-activated protein kinase (AMPK), main intracellular sensor, hyper-activated degenerating neurons several diseases, including AD. In this context, we asked whether AMPK hyper-activation could influence synapses'...
BackgroundMitophagy and mitochondrial dynamics alterations are two major hallmarks of neurodegenerative diseases. Dysfunctional mitochondria accumulate in Alzheimer's disease–affected brains by yet unexplained mechanisms.MethodsWe combined cell biology, molecular pharmacological approaches to unravel a novel pathway which presenilins control phosphatase tensin homolog–induced kinase 1 (Pink-1) expression transcription. In vivo were carried out on various transgenic knockout animals as well...
Abstract The functional preservation of the central nervous system (CNS) is based on neuronal plasticity and survival. In this context, neuroinflammatory state plays a key role involves microglial cells, CNS-resident macrophages. order to better understand contribution neuroprotection, microglia-derived extracellular vesicles (EVs) were isolated molecularly characterized be then studied in neurite outgrowth assays. EVs, mainly composed exosomes microparticles, are an important cell-to-cell...
Alzheimer's disease is characterized by cognitive alterations, cerebral atrophy and neuropathological lesions including neuronal loss, accumulation of misfolded aggregated β-amyloid peptides (Aβ) tau proteins. Iatrogenic induction Aβ suspected in patients exposed to pituitary-derived hormones, dural grafts, or surgical instruments, presumably contaminated with Aβ. Induction has been demonstrated transgenic mice after contamination brain homogenates, very limited functional consequences....
Tauopathies are neurodegenerative disorders characterized by abnormal tau aggregation, with primary 3R (e.g., Picks disease, PiD) and 4R progressive supranuclear palsy, PSP) variants posing a significant diagnostic challenge. Here, we examined brain-derived extracellular vesicles (BD-EVs) isolated from the prefrontal cortex of PiD (3R), PSP (4R), non-demented controls (CTRL) to determine if these reflect disease-specific proteomic signatures. We found that while pathology does not...
Background: Synaptic dysfunction plays an important role in Alzheimer′s disease (AD) and is emerging imaging fluid biomarker. Here, we aimed to assess the regional expression of synaptic vesicle glycoprotein 2A (SV2A) brain extracellular vesicles AD patients its associations with APOE e4 allele, amyloid-&#61538, tau pathologies, other markers. Methods: Mass spectrometry-based synaptosome proteomics was performed on brain-derived (BdEVs) isolated from frontal cortex 17 4 NCs....
<title>Abstract</title> Alzheimer’s disease (AD) is the most prominent form of dementia worldwide. It characterized by tau lesions that spread throughout brain in a spatio-temporal manner. This has led to prion-like propagation hypothesis implicating transfer pathological seeds from cell-to-cell. Human extracellular vesicles isolated brain-derived fluid (BD-EVs) AD patients contain contribute this pathology spreading. Knowing rich diversity EVs, isolation functional EVs sub-population...
In Alzheimer's disease, tau pathology spreads across brain regions as the disease progresses. Intracellular can be released and taken up by nearby neurons. We evaluated single domain anti-tau antibodies, also called VHHs, inhibitors of internalization. identified three VHH uptake: A31, H3-2, Z70mut1. These VHHs compete with membrane protein LRP1, a major receptor mediating neuronal uptake tau. A31 Z70mut1 bind to microtubule binding repeats, which are involved in interaction LRP1. H3-2 is...