A5028151183- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Cholinesterase and Neurodegenerative Diseases
- Memory and Neural Mechanisms
- Ion channel regulation and function
- Genomics and Chromatin Dynamics
- Hippo pathway signaling and YAP/TAZ
- Amyotrophic Lateral Sclerosis Research
- Prion Diseases and Protein Misfolding
- Medicinal Plants and Bioactive Compounds
- Educational and Social Studies
- Neural dynamics and brain function
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Linguistic Studies and Language Acquisition
- Genetics and Neurodevelopmental Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- Stress Responses and Cortisol
- Psychological Treatments and Disorders
- Retinal Development and Disorders
E-Phy-Science (France)
2018-2024
University of Zurich
2006-2016
École Polytechnique Fédérale de Lausanne
2012
ETH Zurich
2008
Université Côte d'Azur
2006
Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification class compounds called ReS19-T, which are able to restore homeostasis in cell-based models tau pathology. Aberrant accumulation leads uncontrolled activation store-operated channels (SOCCs) by remodeling septin filaments at cell cortex. Binding ReS19-T septins restores filament assembly state and restrains entry through SOCCs. In amyloid-β tau-driven mouse disease,...
Chromatin remodeling through histone posttranslational modifications (PTMs) and DNA methylation has recently been implicated in cognitive functions, but the mechanisms involved such epigenetic regulation remain poorly understood. Here, we show that protein phosphatase 1 (PP1) is a critical regulator of chromatin mammalian brain controls PTMs gene transcription associated with long-term memory. Our data PP1 present at cells interacts enzymes machinery including HDAC1 (histone deacetylase 1)...
Amyloid β (Aβ) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and can impair memory hippocampal long-term potentiation (LTP) in vivo vitro . They recognized as the primary neurotoxic agents Alzheimer's disease. The mechanisms underlying such toxicity on synaptic functions complex not fully understood. Here, we provide first evidence that these involve phosphatase 1 (PP1). Using a novel transgenic mouse model expressing human APP with Swedish Arctic...
Abstract Although APP metabolism is being intensively investigated, a large fraction of its modulators yet to be characterized. In this context, we combined two genome-wide high-content screenings assess the functional impact miRNAs and genes on signaling pathways involved. This approach highlighted involvement FERMT2 (or Kindlin-2), genetic risk factor Alzheimer’s disease (AD), as potential key modulator axon guidance, neuronal process that depends regulation metabolism. We found directly...
It has been shown that long-term potentiation (LTP) develops in the connection between mediodorsal thalamus (MD) and medial prefrontal cortex (mPFC) hippocampus (HPC) mPFC following fear extinction, correlates with extinction retention. However, recent lesion studies have combined lesions of MD do not interfere learning retention, while inactivation dorsal HPC disrupts memory. Here we found rats immediate post-training low-frequency stimulation (LFS) suppressed extinction-related LTP...
Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling synaptic strength (Mansuy et al., 1998; Morishita 2001), critically regulates neuroprotective pathways in adult brain. When PP1 is inhibited pharmacologically or genetically, recovery oxygen/glucose deprivation (OGD) vitro , vivo impaired. Furthermore,...
An imbalance between pro-survival and pro-death pathways in brain cells can lead to neuronal cell death neurodegeneration. While such is known be associated with alterations glutamatergic Ca2+ signaling, the underlying mechanisms remain undefined. We identified protein Ser/Thr phosphatase phosphatase-1 (PP1), an enzyme glutamate receptors, as a key trigger of survival that prevent neurodegeneration adult hippocampus. show PP1α overexpression hippocampal neurons limits NMDA receptor...
Neuronal Ca2+ dyshomeostasis and hyperactivity play a central role in Alzheimer's disease pathology progression. Amyloid-beta together with non-genetic risk-factors of contributes to increased influx aberrant neuronal activity, which accelerates neurodegeneration feed-forward fashion. As such, identifying new targets drugs modulate excessive signalling hyperactivity, without overly suppressing them, has promising therapeutic potential.Here we show, using biochemical, electrophysiological,...
The nucleoredoxin gene NXNL2 encodes for two products through alternative splicing, rod-derived cone viability factor-2 (RdCVF2) that mediates neuronal survival and the thioredoxin-related protein (RdCVF2L), an enzyme regulates phosphorylation of TAU. To investigate link between tauopathies, we studied Nxnl2 knockout mouse (Nxnl2−/−). We established expression pattern in brain using a reporter line, characterized behavior Nxnl2−/− at 2 months age. Additionally, long term potentiation...
CHCHD10-related disease causes a spectrum of clinical presentations including mitochondrial myopathy, cardiomyopathy, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We generated knock-in mouse model bearing the p.Ser59Leu (S59L) CHCHD10 variant. Chchd10S59L/+ mice have been shown to phenotypically replicate disorders observed in patients: myopathy with mtDNA instability, cardiomyopathy typical ALS features (protein aggregation, neuromuscular junction degeneration...
NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that under preclinical and clinical development for treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- GluN2A-containing N-methyl-D-aspartate (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in brain. Accordingly, extracellular field potential an enhancement synaptic...
ABSTRACT Although APP metabolism is being intensively investigated, a large fraction of its modulators are yet to be characterized. In this context, we combined two genome-wide high-content screenings assess the functional impact miRNAs and genes on signaling pathways involved. This approach highlighted involvement FERMT2 (or Kindlin-2), genetic risk factor Alzheimer’s disease (AD), as potential key modulator axon guidance; neuronal process that depends regulation metabolism. We found...
Although it is widely accepted that Aβ plays an important role in Alzheimer's disease (AD), the underlying pathogenic mechanisms are still unclear. Recently, smaller oligomeric and protofibrillar aggregates have come into focus several experiments demonstrated a highly neurotoxic effect of these species vitro. The discovery Arctic mutation, familial AD point mutation within sequence APP leading to formation more protofibrils, underscored small oligomers AD. We generated new transgenic mouse...