A5030892223- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Amyotrophic Lateral Sclerosis Research
- Nerve injury and regeneration
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Parkinson's Disease Mechanisms and Treatments
- Microbial Metabolic Engineering and Bioproduction
- Diet and metabolism studies
- Mechanical Circulatory Support Devices
- Exercise and Physiological Responses
- Telomeres, Telomerase, and Senescence
- Congenital heart defects research
- Metabolomics and Mass Spectrometry Studies
- Cardiac Structural Anomalies and Repair
- Regulation of Appetite and Obesity
- Fuel Cells and Related Materials
- Receptor Mechanisms and Signaling
- Lysosomal Storage Disorders Research
- Neuropeptides and Animal Physiology
- Mesenchymal stem cell research
- Congenital Anomalies and Fetal Surgery
Sorbonne Paris Cité
2017-2024
Université Paris Cité
2013-2024
Inserm
2013-2024
Université d'Évry Val-d'Essonne
2024
Laboratoire de Biologie de l'Exercice pour la Performance et la Santé
2021-2023
Toxicologie, Pharmacologie et Signalisation Cellulaire
2021
Délégation Paris 5
2007-2019
Centre National pour la Recherche Scientifique et Technique (CNRST)
2013
Centre National de la Recherche Scientifique
2005-2012
SMN1, the causative gene for spinal muscular atrophy (SMA), plays a housekeeping role in biogenesis of small nuclear RNA ribonucleoproteins. SMN is also present granular foci along axonal projections motoneurons, which are predominant cell type affected pathology. These so-called granules mediate transport specific mRNAs neurites and regulate mRNA localization, stability, as well local translation. Recent work has provided evidence suggesting that may participate assembly granules, but...
Several studies indicate that physical exercise is likely to be neuroprotective, even in the case of neuromuscular disease. In present work, we evaluated efficiency running-based training on type 2 spinal muscular atrophy (SMA)-like mice. The model used this study an SMN (survival motor neuron)-null mouse carrying one copy a transgene human SMN2 . running-induced benefits sustained function and life span SMA-like mice by 57.3%. We showed extent neuronal death reduced lumbar anterior horn...
Several studies using transgenic mouse models of familial amyotrophic lateral sclerosis (ALS) have reported a life span increase in exercised animals, as long animals are submitted to moderate-intensity training protocol. However, the neuroprotective potential exercise is still questionable. To gain further insight into cellular basis exercise-induced effects neuroprotection, we compared efficiency swimming-based training, high-frequency and -amplitude that preferentially recruits fast motor...
Spinal muscular atrophy (SMA) is an inborn neuromuscular disorder caused by low levels of survival motor neuron protein, and for which no efficient therapy exists. Here, we show that the slower rate postnatal motor-unit maturation observed in type 2 SMA-like mice correlated with death. Physical exercise delays death leads to increase motor-units. Furthermore, capable specifically enhancing expression gene encoding major activating subunit NMDA receptor neurons, namely NR2A subunit,...
Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one leading genetic causes death in childhood. SMA caused mutation survival-of-motor-neuron 1 ( SMN1 ) gene, to quantitative defect survival-motor-neuron (SMN) protein expression. All patients retain or more copies SMN 2 modulates disease severity producing small amount stable protein. We reported recently...
Amyotrophic Lateral Sclerosis is an adult-onset neurodegenerative disease characterized by the specific loss of motor neurons, leading to muscle paralysis and death. Although cellular mechanisms underlying ALS-induced toxicity for neurons remain poorly understood, growing evidence suggest a defective energetic metabolism in skeletal muscles participating neuron death ultimately destabilizing neuromuscular junctions. In present study, we report that exercise paradigm, based on high intensity...
Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the selective loss of spinal motor neurons due to depletion survival neuron (SMN) protein. No therapy currently available for SMA, which represents leading genetic cause death in childhood. In present study, we report that insulin-like growth factor-1 receptor (<i>Igf-1r</i>) gene expression enhanced cords SMA-like mice. The reduction expression, either at physiological (through physical exercise) or level, resulted...
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, with typical lifespan of 3–5 years. Altered metabolism key feature ALS that strongly influences prognosis, an increase in whole body energy expenditure and changes skeletal muscle metabolism, including greater reliance on fat oxidation. Dyslipidaemia has been described as part the metabolic dysregulation, but its role pathophysiology disease remains controversial. Among lipids,...
Spinal muscular atrophy (SMA), a lethal neurodegenerative disease that occurs in childhood, is caused by the misexpression of survival motor neuron (SMN) protein neurons. It still unclear whether activating units SMA corrects delay postnatal maturation unit resulting an enhanced neuroprotection. In present work, we demonstrate adequate NMDA receptor activation type 2 mouse model significantly accelerated maturation, counteracted apoptosis spinal cord, and induced marked increase SMN...
The real impact of physical exercise parameters, i.e. intensity, type contraction and solicited energetic metabolism, on neuroprotection in the specific context neurodegeneration remains poorly explored. In this study behavioural, biochemical cellular analyses were conducted to compare effects two different long-term protocols, high intensity swimming low running, motor units a 3 spinal muscular atrophy (SMA)-like mouse model. Our data revealed preferential SMA-induced death intermediate...
Abstract This study establishes a causal link between the limitation of myofibre transitions and modulation calcineurin activity, during different exercise paradigms. We have designed new swimming‐based training protocol in order to draw comparison high frequency amplitude (swimming) low (running). initially analysed time course muscle adaptations 6‐ or 12‐week swimming‐ running‐based program, on two muscles mouse calf, slow‐twitch soleus fast‐twitch plantaris . The magnitude...
Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely vitro, has been demonstrated to have pro-apoptotic role upon induction of death pathway, once translocates nucleus where it facilitates chromatin condensation large scale DNA fragmentation. Given that aif hypomorphic harlequin (Hq) mutant mouse...
Abstract Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from high-calorie diet and sedentary lifestyle, leading to insulin resistance glucose homeostasis perturbation. Physical activity recommended as one first-line treatment in T2DM, but it leads contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription personalized programs specifically designed reverse potential alterations skeletal muscle...
Spinal Muscular Atrophy (SMA), an autosomal recessive neurodegenerative disease characterized by the loss of spinal-cord motor-neurons, is caused mutations on Survival-of-Motor Neuron (SMN)-1 gene. The expression SMN2, a SMN1 gene copy, partially compensates for disruption due to exon-7 excision in 90% transcripts subsequently explaining strong clinical heterogeneity. Several alterations energy metabolism, like glucose intolerance and hyperlipidemia, have been reported SMA at both systemic...
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by survival of motor neuron (SMN) deficiency that induces (MN) degeneration and severe atrophy. Gene therapies increase SMN have proven their efficacy but not for all patients. Here, we explored the unfolded protein response (UPR) status in SMA pathology whether UPR modulation could be beneficial patients.We analysed expression activation key proteins RT-qPCR western blots patient iPSC-derived MNs one cell line which was...
Key points The present study provides evidence that the cardiomyopathy observed in spinal muscular atrophy (SMA) model mice is mainly due to intrinsic cardiac alteration but not autonomic impairment. We demonstrated a non‐pathological sympathetic activity on heart of type 2 SMA‐like mice, which likely counteracts dramatic function, such as arrhythmia and reduced rate. for first time physical exercise partially restores conduction efficiency, prevents fibrosis, attenuates defects protein...
Physical exercise improves motor control and related cognitive abilities reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve synapse as it increases quantal content resistance fatigue, acetylcholine receptors expansion, myocytes' fast-to-slow functional transition. Here, we provide intermediate step between...
Background Obesity is a major public health problem of our time as risk factor for cardiometabolic disease and the available pharmacological tools needed to tackle obesity pandemic are insufficient. Neurotensin (NTS) 13 amino acid peptide, which derived from larger precursor hormone called proneurotensin or Long Form NTS (LF NTS). modulates neuro-transmitter release in central system nervous, facilitates intestinal fat absorption gastrointestinal tract. Mice lacking LF protected high diet...
Abstract The hereditary neurodegenerative disorder spinal muscular atrophy (SMA) is characterized by the loss of cord motor neurons and skeletal muscle atrophy. SMA caused mutations survival neuron (SMN) gene leading to a decrease in SMN protein levels. deficiency alters nuclear body formation whether it can contribute disease remains unclear. Here we screen series small-molecules on patient fibroblasts identify flunarizine that accumulates into Cajal bodies, bodies important for...
Spinal muscular atrophy (SMA) is a fatal neurodegenerative disorder, characterized by motor neuron (MN) degeneration and severe caused Survival of Motor Neuron (SMN) depletion. Therapies aimed at increasing SMN in patients have proven their efficiency alleviating SMA symptoms but not for all patients. Thus, combinational therapies are warranted. Here, we investigated the involvement NADPH oxidase 4 (NOX4) SMA-induced spinal MN death if modulation Nox4 activity could be beneficial patients.We...
<title>Abstract</title> <bold>Background:</bold> Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from high-calorie diet and sedentary lifestyle, leading to insulin resistance glucose homeostasis perturbation. Physical activity recommended as one first-line treatment in T2DM, but it leads contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription personalized programs specifically designed reverse potential...