A5026799853- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Cholinesterase and Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Sperm and Testicular Function
- Parkinson's Disease Mechanisms and Treatments
- Adenosine and Purinergic Signaling
- Prion Diseases and Protein Misfolding
- Dementia and Cognitive Impairment Research
- Tryptophan and brain disorders
- Reproductive Biology and Fertility
- Nerve injury and regeneration
- Amyotrophic Lateral Sclerosis Research
- Regulation of Appetite and Obesity
- Autism Spectrum Disorder Research
- Advanced Proteomics Techniques and Applications
- Memory and Neural Mechanisms
- Pancreatic function and diabetes
- Drug Transport and Resistance Mechanisms
- Neurological diseases and metabolism
- Family and Disability Support Research
- Biochemical effects in animals
Université de Lille
2012-2024
Inserm
2015-2024
Centre Hospitalier Universitaire de Lille
2014-2024
Lille Neurosciences & Cognition
2020-2024
Centre de Recherche Jean Pierre Aubert
2011-2022
Université Lille Nord de France
2011-2015
Predict (France)
2011-2012
The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, fibrillization of impair synaptic plasticity cause degeneration. However, pathology may also result in the loss specific physiological functions, which largely unknown but could contribute to neuronal dysfunction. In present study, we uncovered a novel function its ability regulate brain insulin...
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...
Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk developing Alzheimer's disease (AD) and mitigates both amyloid Tau lesions in transgenic mouse models disease. While short-term treatment with A2AR antagonists have been shown to alleviate cognitive deficits amyloidogenesis, impact chronic long-term on development burden, associated neuroinflammation memory has never assessed. In present study, we evaluated effect 6-month APPsw/PS1dE9 mice...
See Cunha (doi:10.1093/brain/awz335) for a scientific commentary on this article. Carvalho et al. provide clues to the onset of immune dysregulation underlying early synaptic loss in Alzheimer’s disease and tauopathies, by linking overactivation adenosine A2A receptors tau pathology particular microglial signature (upregulation C1q TREM2) allied glutamatergic synapses cognitive deficits.
At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel postpubertal decrease hypothalamic as well extrahypothalamic expression of master molecule controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance microRNA-gene network known regulate GnRH neuron maturation together with altered...
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...
Caffeine is the most widely consumed psychoactive substance in world. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed mechanisms associated with habitual (chronic) caffeine mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic exerts concerted pleiotropic effects at epigenomic, proteomic, and metabolomic levels. lowered metabolism-related processes (e.g., level of metabolomics gene expression)...
Brief summary: This study identified a new role for GnRH in higher brain function using rodent model of Down Syndrome. It reports the first time an improvement cognitive functions patients with Syndrome treated pulsatile GnRH.
The τ pathology found in Alzheimer disease (AD) is crucial cognitive decline. Midlife development of obesity, a major risk factor insulin resistance and type 2 diabetes, increases the dementia AD later life. impact obesity on has been suggested to be related central resistance, secondary peripheral resistance. effects diet-induced (DIO) remain unknown. In this study, we evaluated high-fat diet, given at an early pathological stage, THY-Tau22 transgenic mouse model progressive AD-like...
Abstract Mitochondria dysfunctions and mitophagy failure have been associated with several Alzheimer’s disease (AD) related molecular actors including amyloid beta (Aβ) recently the precursor protein-C terminal fragments (APP-CTFs). The efficacy of process in neurons relies on regulated mitochondrial transport along axons involving a complex machinery. contribution protein (APP) its derived to machinery alterations AD not investigated before. We report herein change expression proteins (SNPH...
Muscleblind-like-1 (MBNL1) is a splicing regulatory factor controlling the fetal-to-adult alternative transitions during vertebrate muscle development. Its capture by nuclear CUG expansions one major cause for type 1 myotonic dystrophy (DM1). Alternative produces MBNL1 isoforms that differ presence or absence of exonic regions 3, 5, and 7. To understand better their respective roles consequences deregulation expression in DM1, here we studied constitutive exons. By combining genetics,...
While the spatiotemporal development of Tau pathology has been correlated with occurrence cognitive deficits in Alzheimer's patients, mechanisms underlying these remain unclear. Both brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB play a critical role hippocampus-dependent synaptic plasticity memory. When applied on hippocampal slices, BDNF is able to enhance AMPA receptor-dependent basal transmission through mechanism involving N-methyl-d-Aspartate receptors...
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....
Alzheimer's disease is the most common form of dementia characterized by intracellular aggregates hyperphosphorylated Tau protein and extracellular accumulation amyloid β (Aβ) peptides. We previously demonstrated that purinergic receptor P2X7 (P2X7) plays a major role in Aβ-mediated neurodegeneration but relationship between remained overlooked. Such link was supported cortical upregulation patients with various type frontotemporal lobar degeneration, including mutation Tau-coding gene,...
Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral angiopathy resulting brain hemorrhages and devastating clinical impacts. Iatrogenic of tau is also suspected but not experimentally proven. In both scenarios, lesions were detected several decades after the putatively triggering medico-surgical act. There however little information regarding cognitive repercussions individuals...
Early pathological upregulation of adenosine A2A receptors (A2ARs), one the caffeine targets, by neurons is thought to be involved in development synaptic and memory deficits Alzheimer's disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal A2AR hippocampus APP/PS1 mice developing AD-like amyloidogenesis. Our findings revealed that early presence an ongoing amyloid pathology exacerbates impairments mice. These behavioural changes were not linked...
The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). Preventing deregulated APP processing by inhibiting amyloidogenic of carboxy-terminal fragments (APP-CTFs), and reducing the toxic effect beta (Aβ) peptides remain an effective therapeutic strategy. We report design piperazine-containing compounds derived from chloroquine structure evaluation their effects on metabolism ability to modulate APP-CTF production Aβ peptide. Compounds which retained alkaline...
Abstract Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types lesions occur form neuropil threads, neurofibrillary tangles, neuritic i.e. aggregates within neurites surrounding Aβ deposits. The cascade events linking these synaptic or memory impairments are still debated. Intracerebral infusion human AD brain extracts plaque-bearing mice do not overexpress...
Reduction of Tau protein expression was described in 2003 by Zhukareva et al. a variant frontotemporal lobar degeneration (FTLD) referred to as diagnosis dementia lacking distinctive histopathology, then re-classified FTLD with ubiquitin inclusions. However, the analysis has not been reconsidered since then. Knowledge molecular basis aggregates and genes that are mutated spectrum would enable determine whether "Tau-less" is separate pathological entity or if it belongs an existing subclass...