A5051897401- Liver physiology and pathology
- Alzheimer's disease research and treatments
- Cell death mechanisms and regulation
- PI3K/AKT/mTOR signaling in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammasome and immune disorders
- S100 Proteins and Annexins
- Protein Kinase Regulation and GTPase Signaling
- Phagocytosis and Immune Regulation
- Endoplasmic Reticulum Stress and Disease
- Cancer Mechanisms and Therapy
- Axon Guidance and Neuronal Signaling
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Angiogenesis and VEGF in Cancer
- Metal complexes synthesis and properties
- Peptidase Inhibition and Analysis
- Fibroblast Growth Factor Research
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
Jewish General Hospital
2013-2021
McGill University
2013-2021
Institut de Biologie de Lille
2006-2012
Institut Pasteur de Lille
2006-2012
Centre National de la Recherche Scientifique
2006-2012
Université de Lille
2006-2012
Université Lille Nord de France
2009
Inserm
2009
Alzheimer's disease (AD) is an intractable progressive neurodegenerative characterized by cognitive decline and dementia. An inflammatory pathway, involving Caspase-1 activation, associated with human age-dependent impairment several classical AD brain pathologies. Here, we show that the nontoxic blood-brain barrier permeable small molecule inhibitor VX-765 dose-dependently reverses episodic spatial memory impairment, hyperactivity in J20 mouse model of AD. Cessation results reappearance...
Abstract Early therapeutic interventions are essential to prevent Alzheimer Disease (AD). The association of several inflammation-related genetic markers with AD and the early activation pro-inflammatory pathways in suggest inflammation as a plausible target. Inflammatory Caspase-1 has significant impact on AD-like pathophysiology inhibitor, VX-765, reverses cognitive deficits mouse models. Here, one-month pre-symptomatic treatment Swedish/Indiana mutant amyloid precursor protein (APP Sw/Ind...
Hepatocyte growth factor/scatter factor (HGF/SF) acts through the membrane-anchored Met receptor tyrosine kinase to induce invasive growth. Deregulation of this signaling is associated with tumorigenesis and involves, in most cases, overexpression receptor. We demonstrate that processed epithelial cells by presenilin-dependent regulated intramembrane proteolysis (PS-RIP) independently ligand stimulation. The proteolytic process involves sequential cleavage metalloproteases gamma-secretase...
Understanding the regulatory mechanisms mediating PRNP gene expression is highly relevant to elucidating normal cellular prion protein (PrP) function(s) and transmissibility of neurodegenerative diseases. Here, luciferase reporter assays showed that an endoplasmic reticulum stress element (ERSE)-like element, CCAAT-N26-CCACG in human promoter, regulated by ER X-box-binding 1 (XBP1) but not activating transcription factor 6 α (ATF6α). Bioinformatics identified ERSE-26 motif 37 other genes...
Abstract The receptor tyrosine kinase Met and its ligand, the hepatocyte growth factor/scatter factor, are essential for embryonic development, whereas deregulation of signaling pathways is associated with tumorigenesis metastasis. presenilin‐regulated intramembrane proteolysis ( PS‐RIP ) involved in ligand‐independent downregulation Met. This proteolytic process involves shedding extracellular domain followed by γ‐secretase cleavage, generating labile intracellular fragments degraded...
Abstract Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via oxidation their active site cysteine. and derivatives, azure A B competitively inhibited recombinant Caspase-6 (Casp6) Casp6 activity transfected human colon carcinoma cells serum-deprived primary neuron cultures. also Casp1 Casp3. Furthermore,...
Abnormally elevated hippocampal Caspase-6 (Casp6) activity is intimately associated with age-related cognitive impairment in humans and mice. In humans, these high levels of Casp6 are initially localized the entorhinal cortex, area brain first affected by formation neurofibrillary tangles, according to Braak staging. The reason for vulnerability cortex neurons tangle pathology unknown. involved axonal degeneration, therefore, one possibility explain increased would be that afferent olfactory...
The transcriptional repressor <i>HIC1</i> (Hypermethylated in Cancer 1) is a tumor suppressor gene inactivated many human cancers including breast carcinomas. In this study, we show that HIC1 direct of β-2 adrenergic receptor (<i>ADRB2</i>). Through promoter luciferase activity, chromatin immunoprecipitation (ChIP) and sequential ChIP experiments, demonstrate <i>ADRB2</i> target HIC1, endogenously WI-38 cells following re-expression cancer cells. Agonist-mediated stimulation ADRB2 increases...
The tumor suppressor gene hypermethylated in cancer 1 (HIC1), which encodes a transcriptional repressor, is epigenetically silenced many human tumors. Here, we show that ectopic expression of HIC1 the highly malignant MDA-MB-231 breast cell line severely impairs proliferation, migration, and invasion vitro. In parallel, infection lines with retrovirus expressing also induces decreased mRNA protein tyrosine kinase receptor EphA2. Moreover, chromatin immunoprecipitation (ChIP) sequential ChIP...
Caspase-6 is an effector caspase that has not been investigated thoroughly despite the fact strongly activated in Alzheimer disease brains. To understand full physiological impact of humans, we expression. We performed western blot analyses to detect pro-Caspase-6 and its active p20 subunit fetal adult lung, kidney, brain, spleen, muscle, stomach, colon, heart, liver, skin, adrenals tissues. The levels were semi-quantitated by densitometry. results show a ubiquitous expression most tissues...
Alzheimer's disease (AD) occurs as either an autosomal dominant inherited or sporadically. While familial mutant genes can be expressed in cells animal models to assess dysregulated functions, sporadic AD cannot replicated given our lack of understanding causality. Fur thermore, the study forms is difficult inaccessibility brain tissues living individuals and manifestation symptoms years after onset disease. Here, objective was if induced pluripotent stem cell-derived neurons from...
Abstract Active Caspase-6 (Casp6) and Tau cleaved by Casp6 at amino acids 402 (Tau∆D402) 421 (Tau∆D421) are present in early Alzheimer disease intraneuronal neurofibrillary tangles, which made primarily of filamentous aggregates. To assess whether cleavage contributes to pathology Casp6-mediated age-dependent cognitive impairment, we generated transgenic knock-in mouse models that conditionally express full-length human (hTau) 0N4R only (CTO) or together with (hCasp6) (CTC). Region-specific...
Caspases play an important role in maintaining tissue homeostasis. Active Caspase-6 (Casp6) is considered a novel therapeutic target against Alzheimer disease (AD) since it present AD pathological brain lesions, associated with age-dependent cognitive decline, and causes impairment the mouse brain. However, active Casp6 highly expressed activated normal human colon epithelial cells raising concerns that inhibiting may promote carcinogenesis. Furthermore, others have reported rare mutations...
Methylene blue is a well-tolerated treatment for many conditions in humans and currently being tested phase 3 clinical trials Alzheimer Disease as Tau aggregation inhibitor. oxidizes cysteine residues on protein to inhibit its oligomerization. The Caspase-6 protease has been implicated axonal degeneration cognitive impairment AD. Whether methylene can also caspases by oxidation of the catalytic unknown. Inhibition recombinant active Caspase-1, Caspase-3, derivatives, azure A B, was...
Abstract: Hepatocyte growth factor/scatter factor (HGF/SF) induces scattering, morphogenesis, and survival of epithelial cells through activation the MET tyrosine kinase receptor. HGF/SF are involved in normal development tumor progression many tissues organs, including mammary gland. In order to find target genes its function, we used an oligonucleotide microarray representing 1,920 known be apoptosis, transcriptional regulation, signal transduction. MCF‐10A human were grown absence serum...