A5029499808- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Medicinal Plants and Neuroprotection
- Neuroinflammation and Neurodegeneration Mechanisms
- Cannabis and Cannabinoid Research
- Genetics and Neurodevelopmental Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Cell death mechanisms and regulation
- Phytochemicals and Medicinal Plants
- Tryptophan and brain disorders
- Calpain Protease Function and Regulation
- Gene expression and cancer classification
- Biochemical effects in animals
- RNA Research and Splicing
- GABA and Rice Research
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Muscle Physiology and Disorders
- Nuclear Receptors and Signaling
Observatoire de Paris
2020-2025
Institut du Cerveau
2013-2025
Inserm
2010-2025
Sorbonne Université
2013-2025
Centre National de la Recherche Scientifique
2000-2025
Assistance Publique – Hôpitaux de Paris
2008-2023
Université Paris Cité
2010-2023
Sorbonne Paris Cité
2023
Pitié-Salpêtrière Hospital
2023
Institute for Neurodegenerative Disorders
2016
Parkinson's disease is a neurodegenerative proteinopathy that primarily affects mesencephalic dopaminergic neurons. This depletion can be phenotypically reproduced in various experimental models through the administration of two neurotoxins: N-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA). The mechanisms underlying cell death processes induced by these toxins remain subject debate. In this context, studies suggest oxidative-stress-related may contribute to dysfunction...
Striatal cell death in Huntington's Disease (HD) may involve mitochondrial defects, NMDA-mediated excitotoxicity, and activation of effector proteases such as caspases calpain. However, the precise contribution defects these HD is unknown. Here, we addressed this question by studying mechanism striatal rat models using complex II inhibitor 3-nitropropionic acid (3-NP). The neurotoxin was either given intraperitoneal injections (acute model) or over 5 d constant systemic infusion osmotic...
N-acetylaspartate (NAA) quantification by 1 H-magnetic resonance spectroscopy has been commonly used to assess in vivo neuronal loss neurodegenerative disorders. Here, the authors ex and rat primate models of progressive striatal degeneration induced mitochondrial toxin 3-nitropropionate (3NP) determine whether early NAA depletions could also be associated with dysfunction. In rats that were treated for 3 days 3NP had motor symptoms, found a significant decrease concentrations, specifically...
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due its anti-inflammatory properties. More recently, an additional mechanism which doxycycline may exert effects has been as it shown that inhibits amyloid aggregation. Here, we studied on aSyn in vivo, vitro cell free system using...
The role of caspases and calpains in neurodegeneration remains unclear. In this study, we focused on these proteases a rat model Huntington's disease using the mitochondrial toxin 3-nitropropionic acid (3NP). Results showed that 3NP-induced death striatal neurons was preceded by cytochrome c redistribution, transient caspase-9 processing, activation calpain, whereas levels active/processed form caspase-3 remained low were even reduced as compared with control animals. We evidenced here...
Cannabinoids could provide neuroprotection in neurodegenerative disorders. In this study, we examined whether a treatment with Delta9-tetrahydrocannabinol, non-selective cannabinoid receptor agonist, or SR141716, selective antagonist for the CB(1) subtype, affect toxicity of complex II reversible inhibitor malonate injected into striatum, which replicates mitochondrial deficiency seen Huntington's disease patients. As expected, injection produced significant reduction cytochrome oxidase...
According to the "indirect" excitotoxicity hypothesis, mitochondrial defects increase Ca2+ entry into neurons by rendering NMDA-R hypersensitive glutamate. We tested this hypothesis investigating in rat striatum and cultured striatal cells how partial complex II inhibition produced 3-nitropropionic acid (3NP) modifies toxicity of agonist quinolinate (QA). showed that nontoxic 3NP treatment, leading activity, greatly exacerbated degeneration slightly toxic QA treatment through an...
Although prion propagation is well understood, the signaling pathways activated by neurotoxic forms of protein (PrP) and those able to mitigate pathological phenotypes remain largely unknown. Here, we identify src-2 , a Fyn-related kinase, as gene required for human PrP with an insertional mutation be in Caenorhabditis elegans, longevity modulator sir-2.1 /SIRT1, sirtuin deacetylase, modifier neurotoxicity. The expression octarepeat-expanded C. elegans mechanosensory neurons led progressive...
Several neurotransmitter systems are involved in the pathogenesis of Huntington's disease. Here, we examined involvement cannabinoid CB1 receptors striatal degeneration rat model this disease generated by administration 3-nitropropionic acid (3NP). days before onset degeneration, G-protein activation agonists was significantly decreased whereas density and mRNA levels remained essentially normal. This change transient, recovering full functionality after few days. Later, at profound...
Chlordecone (CLD) is an organochlorine pesticide (OCP) that currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase risk of Parkinson's disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics Parkinsonism-like neurodegeneration. For that, used culture systems mouse midbrain dopamine (DA) neurons and glial cells, together nematode C. elegans as vivo model organism. We established...
Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD), disorder caused by an abnormal expansion of polyglutamine tract the protein huntingtin (Htt), aging is unclear. For given length, probability onset increases with age. There are mainly two hypotheses that could explain adult HD: Either mutant Htt progressively produces cumulative defects over time or "normal" renders neurons more vulnerable to toxicity. present study, we directly explored whether affected...
In prion diseases, a major issue in therapeutic research is the variability of effect between strains. Stimulated by report an antiprion scrapie model and ongoing international clinical trials using doxycycline, we studied efficacy cyclines against propagation human prions. First, successfully propagated various Creutzfeldt-Jakob disease (CJD) isolates (sporadic, variant, iatrogenic CJD) neuronal cultures expressing protein. Then, found that doxycycline was most effective compound, with...
Transcriptome analysis of mammalian brain structures is a potentially powerful approach in addressing the diversity cerebral functions. Here, we used microassay for serial gene expression (SAGE) to generate quantitative mRNA profiles normal adult mouse striatum, nucleus accumbens, and somatosensory cortex. Comparison these revealed 135 transcripts heterogeneously distributed brain. Among them, majority (78), although matching registered sequence, are novel regional markers. To improve...
A tetrahydroisoquinoline identified in Mucuna pruriens ((1R,3S)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-1,3-dicarboxylic acid, compound 4) was synthesized and assessed for its vitro pharmacological profile vivo effects two animal models of Parkinson's disease. Compound 4 inhibits catechol-O-methyltransferase (COMT) with no affinity the dopaminergic receptors or dopamine transporter. It restores dopamine-mediated motor behavior when it is co-administered L-DOPA to C. elegans...
Human prion diseases are fatal neurodegenerative disorders that include sporadic, infectious and genetic forms. Inherited Creutzfeldt-Jakob disease due to the E200K mutation of protein-coding gene is most common form disease. The phenotype resembles sporadic at both clinical pathological levels, with a median duration 4 months. To date, there no available treatment for delaying occurrence or slowing progression human diseases. Existing in vivo models do not allow high-throughput approaches...
Abstract Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due its anti-inflammatory properties. More recently, an additional mechanism which doxycycline may exert effects has been as it shown that inhibits amyloid aggregation. Here, we studied on aSyn in vivo, vitro cell free system...