A5046524146- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Sperm and Testicular Function
- Cholinesterase and Neurodegenerative Diseases
- Reproductive Biology and Fertility
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Dementia and Cognitive Impairment Research
- Muscle Physiology and Disorders
- Amyotrophic Lateral Sclerosis Research
- Nerve injury and regeneration
- Computational Drug Discovery Methods
- Amyloidosis: Diagnosis, Treatment, Outcomes
- 14-3-3 protein interactions
- Animal Genetics and Reproduction
- Endoplasmic Reticulum Stress and Disease
- Fibroblast Growth Factor Research
- Signaling Pathways in Disease
- S100 Proteins and Annexins
Inserm
2016-2025
Université de Lille
2015-2025
Centre Hospitalier Universitaire de Lille
2010-2023
Lille Neurosciences & Cognition
2021-2023
Centre de Recherche Jean Pierre Aubert
2011-2021
Centre de Recherche en Myologie
2019
Université Lille Nord de France
2009-2017
Institut de Médecine et d'Epidémiologie Africaines
2003-2012
Northwestern University
2012
Williams & Associates
2012
To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and different stages AD.The pathophysiologic significance AD lesions, namely amyloid plaques tangles, is still unclear, especially their interrelationship link with cognitive impairment.The study included 130 patients various ages statuses, from nondemented control subjects (n = 60, prospective study) to severe definite AD. Paired helical filaments (PHF)-tau Abeta were used as biochemical histologic...
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...
Type III RNase Dicer is responsible for the maturation and function of microRNA (miRNA) molecules in cell. It now well-documented that fine-tuning miRNA gene network are important neuronal integrity. However, underlying mechanisms involved death, particularly adult brain, remain poorly defined. Here we show absence forebrain accompanied by a mixed neurodegenerative phenotype. Although loss observed hippocampus, cellular shrinkage predominant cortex. Interestingly, degeneration coincides with...
Alzheimer's disease (AD) and related tauopathies comprise a large group of neurodegenerative diseases associated with the pathological aggregation tau protein. While much effort has focused on understanding function tau, little is known about endogenous mechanisms regulating metabolism in vivo how these contribute to disease. Previously, we have shown that microRNA (miRNA) cluster miR-132/212 downregulated such as AD. Here, report deficiency mice leads increased expression, phosphorylation...
Abstract : Pathological tau prroteins that constitute the basic matrix of neuronal inclusions observed in numerous neurodegenerative disorders are disease specific. This is mainly consequence aggregation specific sets isoforms according to diseases, i.e., six Alzheimer's (AD) and exclusively three lacking corresponding sequence exon 10 (E10‐) Pick's (PiD). By using antibodies different one‐ two‐dimensional gel electrophoresis followed by western blots, we demonstrate herein a third group...
Intraneuronal aggregates of hyperphosphorylated tau proteins, referred to as pathological tau, are found in brain areas demented patients affected by numerous different neurodegenerative disorders. We previously described a particular biochemical profile proteins myotonic dystrophy type 1 (DM1). This multisystemic disorder is characterized an unstable CTG repeat expansion the 3′-untranslated region DM protein kinase gene. In human central nervous system, consist six isoforms that differ...
Abstract Aggregated τ proteins constitute the basic matrix of neuronal inclusions specific to numerous neurodegenerative disorders. Monodimensional and two‐dimensional Western blot analyses performed on cortical brain homogenates allowed discrimination between disease‐specific protein profiles. These observations raised issue physiopathological significance such specificities. Alzheimer's disease (AD) pathological (PTPs) (τ 74, 69, 55) were compared with those Pick's (PiD) 64, using a panel...
The autosomal dominant mutation causing myotonic dystrophy (DM1) is a CTG repeat expansion in the 3′-UTR of DM protein kinase (DMPK) gene. This multisystemic disorder includes myotonia, progressive weakness and wasting skeletal muscle extramuscular symptoms such as cataracts, testicular atrophy, endocrine cognitive dysfunction. mechanisms underlying its pathogenesis are complex. Recent reports have revealed that DMPK gene haploinsufficiency may account for cardiac conduction defects whereas...
Pick's disease (PiD) is characterized by a pan-laminar frontotemporal cortical atrophy, widespread degeneration of the white matter, chromatolytic neurons, and Pick bodies (PB). Microtubule-associated Tau proteins are main cytoskeletal components modified during these neurodegenerative changes. In present study, pathological alterations were investigated in brains five PiD cases at both neuropathological biochemical levels, using monoclonal antibody AD2 which recognizes...
Abstract Vaccination against human beta‐amyloid peptide (Aβ) has been shown to remove the amyloid burden produced in transgenic mice overexpressing mutated precursor protein (APP) gene. For beings, efficiency of this therapeutic strategy take into account specificities amyloid, especially at early stages ‘sporadic’ Alzheimer's disease (AD). Aβ 40/42 were previously quantified tissues from our well‐established brain bank, including non‐demented individuals with both mild and tau pathologies,...
There is a growing interest in the involvement of anesthetic agents etiology postoperative cognitive dysfunction. Recent animal studies suggest that acute anesthesia induces transient hyperphosphorylation tau, an effect essentially ascribed to hypothermia. The main aim present study was investigate effects, normothermic conditions, or repeated exposure sevoflurane, halogenated agent, on hippocampal tau phosphorylation and spatial memory adult mice.5 6-month-old C57Bl6/J mice were submitted...
Amyloid precursor protein (APP) metabolism is central to the pathogenesis of Alzheimer disease. We showed recently that amyloid intracellular domain (AICD), which released by γ-secretase cleavage APP C-terminal fragments (CTFs), strongly increased in cells treated with alkalizing drugs (Vingtdeux, V., Hamdane, M., Bégard, S., Loyens, A., Delacourte, Beauvillain, J.-C., Buée, L., Marambaud, P., and Sergeant, N. (2007) Neurobiol. Dis. 25, 686–696). Herein, we aimed determine cell compartment...
Recent data indicate that Tau immunotherapy may be relevant for interfering with neurofibrillary degeneration in Alzheimer disease and related disorders referred to as Tauopathies. The key question is the choice of epitope target. Abnormal phosphorylation a well-described post-translational modification proteins good In present study, we investigated effects active immunization against pathological phospho-Ser422 THY-Tau22 transgenic mouse model. Starting from 3-6 months age, mice develop...
Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk developing Alzheimer's disease (AD) in humans and mitigates both amyloid Tau burden transgenic mouse models. However, impact selective A2AR blockade on progressive development AD-related lesions associated memory impairments has not been investigated. In present study, we removed gene encoding from THY-Tau22 mice analysed subsequent effects pathological (Tau phosphorylation aggregation,...
Tauopathies represent a large class of neurological and movement disorders characterized by abnormal intracellular deposits the microtubule-associated protein tau. It is now well established that mis-splicing tau exon 10, causing an imbalance between three-repeat (3R) four-repeat (4R) isoforms, can cause disease; however, underlying mechanisms affecting splicing in neurons remain poorly understood. The small noncoding microRNAs (miRNAs), known for their critical role posttranscriptional gene...
For some neurological disorders, disease is primarily RNA mediated due to expression of non-coding microsatellite expansion RNAs (RNA(exp)). Toxicity thought result from enhanced binding proteins these expansions and depletion their normal cellular targets. However, experimental evidence for this sequestration model lacking. Here, we use HITS-CLIP pre-mRNA processing analysis human control versus myotonic dystrophy (DM) brains provide compelling toxicity model. MBNL2 binds directly DM repeat...
Microtubule-associated Tau proteins are major actors in neurological disorders, the so-called tauopathies. In some of them, and specifically Alzheimer's disease (AD), hyperphosphorylated forms aggregate into neurofibrillary tangles. Following understanding complexity Tau's molecular profile with its multiple isoforms post-translational modifications represent an important issue, a analytical challenge. Immunodetection methods are, fact, limited by number, specificity, sensitivity, capturing...
Abstract Tau is a central player in Alzheimer's disease (AD) and relatedTauopathies, where it found as aggregates degenerating neurons. Abnormalpost-translational modifications, such truncation, are likely involved thepathological process. A major step forward understanding the role of Tautruncation would be to identify precise cleavage sites several truncatedTau fragments that observed until now AD brains, especially those truncatedat N-terminus, which less characterized than truncated at...
Since the discovery of prion diseases, concept has emerged that a protein could be transmissible pathogen. As such, this pathogen agent can transfer its pathological mis-folded shape to same but normally folded thus leading propagation disease. This idea is now extrapolated several neurological diseases associated with mis-folding and aggregation, such as Alzheimer's disease (AD). AD slowly developing dementing characterized by coexistence two types lesions: parenchymal amyloid deposits...