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Evaluation of the anti-inflammatory and neuroprotective effects of an alpha 7 nicotinic acteylcholine receptor agonistin an in vivo neuroinflammatory rat model
Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. To date, the management of patients with neurodegenerative diseases is based on symptomatic treatments. In recent years, the scientific community has focused its research on the regulation of the neuroinflamma...
Biological mechanisms driving neurodegeneration in Multiple Sclerosis : an in vivo approach combining positron emission tomography and high field magnetic resonance imaging
Multiple Sclerosis (MS), an inflammatory and demyelinating disease of the central nervous system, is the leading cause of non-traumatic neurological disability in young adults in western countries. It is now well accepted that neurodegeneration is the key mechanism underlying disability progression...
Consequences of imd pathway activation during metamorphosis and adult life of drosophila
Upon infection, the intensity and duration of the immune response must be tightly controlled at the risk of becoming harmful for the host. In the fruit fly Drosophila Melanogaster, a bacterial infection leads to the activation of evolutionary conserved NFk-B signalling pathways, through detection of...
Characterisation of Transgenic C. elegans Alzheimer models, expressing the Human Tau protein in their GABAergic motonones
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by two hallmarks: extracellular plaques composed of amyloid-β (Aβ) deposits and intraneuronal accumulation of hyper and abnormal phosphorylated tau, also called neurofibrillary tangles (NFT). Despite many decades of research, the...
New aspects of the biology of the prion protein
Transmissible spongiform encephalopathies form a group of fatal neurodegenerative disorders represented principally by Creutzfeldt-Jakob disease in humans, and by scrapie and bovine spongiform encephalopathy in animals. Also called prion diseases, these disorders are infectious, sporadic, or genetic...
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Rescue of cognitive aging by long-lasting environmental enrichment exposure initiated before median lifespan.
International audience The rescue of cognitive function through environmental enrichment (EE) during aging has been extensively documented. However, the age at onset, the duration of EE, and the cerebral mechanisms required to obtain the greatest benefits still remain to be determined. We have recen...
Demographic study and CoDE-Seq analysis of rare neurodegenerative diseases with motor expression in Martinique
Rare Neurodegenerative Diseases with Motor Expression (RNDME) are a very heterogeneous group of neurodegenerative pathologies of acquired or innate physiopathology that can occur at any age. They have a targeted impact on the central or peripheral neurological structures involved in motor activity....
Study of the role of a new striatal marker in the neurodegenerescence of Huntington's disease
DCLK3 (Doublecortin-like kinase 3) is a neuronal kinase enriched in the striatum and in the dentate gyrus of the hippocampus. DCLK3 expression is markedly reduced in the brain of Huntington’s disease (HD) patients. However, its role remains unknown. The laboratory previously showed that DCLK3 could...
The prion-like properties of the mutant huntingtin protein : demonstration in in vitro and in vivo systems
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that affects approximately 3 - 8 people in 100,000 individuals worldwide. HD is caused by a mutation in the HTT gene, which codes for the protein huntingtin (HTT), consisting of an expansion of 35 CAG repeats in the exon 1...
The role of insulin in retinal ganglion cell dendrite and synapse regeneration after optic nerve injury : molecular mechanisms and potential therapeutic targets
Glaucoma, just as many other neurodegenerative diseases, triggers neuronal death and remained incurable, hence representing a heavy burden for the society. Therefore, there is a critical need for developing new therapeutic strategies to delay the progression of and, ultimately, cure neurological con...
Impact of TP53INP1 deficiency on nigral dopaminergic neurodegeneration under normal ageing- and Parkinson’s disease-related stress conditions
The stress-induced protein TP53INP1 acts as a dual positive regulator of transcription and of autophagy. Its deficiency has been linked with cancer and metabolic syndrome via mechanisms common to those involved in neurodegenerative diseases, including altered autophagy, oxidative stress and chronic...
Impacts of circadian clock disruptions on age-related functional decline in Drosophila melanogaster
Long-term disruption of circadian clocks, as occurs often in our "24/7 societies", can be detrimental. These clocks control self-sustained biological rhythms with ~24h periodicity and synchronize to the daily light-dark cycle. Clock disruption may impact normal brain aging as well as Parkinson disea...
Role of the Glycogen Synthase Kinase 3 for the Retinal Development and Homeostasis
Post-translational modifications (PTMs) allow a higher degree of regulation for the control of gene expression by generating functional diversity at the proteome level. In the central nervous system, PTMs regulate stability or activity of transcription factors allowing a rapid response to external s...
Characterization of pharmacological modulators and study of ASIC activation with cysteine-based cross-linking
Acid-sensing ion channels (ASICs) are proton-gated, voltage-insensitive Na+ channels that are localized in the central and the peripheral nervous system participating in a range of physiological and pathological functions such as pain sensation, learning and memory, fear, and neurodegeneration after...
Huntington's disease, gene network, transcriptomics analysis, computational biology, spectral graph theory, neurodegenerative mechanisms
Huntington’s disease is a hereditary neurodegenerative disease that has become a model to understand physiopathological mechanisms associated to misfolded proteins that ocurs in brain diseases. Despite exciting findings that have uncover pathological mechanisms occurring in this disease and that mig...
ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues
International audience Background: Monogenetic forms of amyotrophic lateral sclerosis (ALS) offer an opportunity for unraveling the molecular mechanisms underlying this devastating neurodegenerative disorder. In order to identify a link between ALS-related metabolic changes and neurodegeneration, we...
Role of the protein cellular prion ( PRPC) in the neural differentiation : prions infection( PRPC) and molecular base of the neurodegenerescence
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Neurodegeneration and compensatory process in the brain of rodents following damage to the nigro-striated dopaminergic system and effects of high frequency subthalamic nucleus stimulation
The compensatory processes that accompany a lesion of the nigrostriatal dopaminergic (DA-ergic) system serve to maintain its function and illustrate adult brain neuroplasticity. The typical motor symptoms of Parkinson’s diseases (PD), characterized by progressive degeneration of DA-ergic neurons of...
Reticular stress in the Alzheimer's disease : role of the XBP-1s transcription factor
Alzheimer's disease is a neurodegenerative pathology strongly correlated to aging. Its symptoms are characterized by an impaired short term memory process in the early stages of the disease and later on by a loss of all type of memory process. There is actually no cure for this pathology. At the his...
Impact of glutaminergic excitotoxity on amyloid pathology and the role of different blood monocytes subtypes in this process
A large number of processes are responsible for the proper functioning of living organisms. These are provided among others by mechanisms for self defence, cleaning and regulation in order to maintain the environment stable. When one or more of these mechanisms are lacking, some clinical pathology c...
Probing of glucidic biomarkers of mucopolysaccharidosis and physiopathology study
The identification of biomarkers remains one of the main challenges for analytical sciences and a major stake for clinical research. Glycosaminoglycans (GAGs) have been identified as potential biomarkers of mucopolysaccharidoses (MPS) belonging to rare genetic diseases with often a deadly issue. The...
Studies on the Role of Cellular Heparan Sulfate on Tau Pathology in Alzheimer's Disease and Related Tauopathies
According to its higher prevalence worldwide among all dementia cases, Alzheimer's disease (AD) is placed as the first pathology affecting people aged of more than 65 years old. Since it first description in 1907, profound research and groundbreaking observations have been made concerning the histop...
Influence of anxiety in spatial memory impairments related to the loss of vestibular function in rat.
International audience It is now well established that vestibular information plays an important role in spatial memory processes. Although vestibular lesions induce anxiety in humans, this finding remains controversial in rodents. However, it is possible that anxiety-related behavior is associated...
Involvement of Kv3.1 potassium chanels in 7-ketocholesterol, 24S-hydroxycholesterol and C24 : 0-induced lipotoxicity on 158N and BV-2 cells : relationships between KV3.1 homeostasis, peroxisomal metabolism and Alzheimer's disease
Potassium (K+) is involved in the regulation of cellular excitability, cell cycle regulation, cell viability, neuroprotection and maintenance of microglial and oligodendrocytic functions. Potassium dysfunction, described in several neurodegenerative diseases such as Alzheimer's Disease (AD), multipl...
Design, synthesis and biological evaluation of MT5-MMP inhibitors : a new biological target with potential interest for Alzheimer’s disease
Alzheimer's disease (AD), the most common form of dementia, is a neurodegenerative and incurable brain disorder, for which only 4 symptomatic treatments are available at this time. Because of the heavy economic and societal impacts, there is an urgent need to find new treatments that target the mole...