A5023172892- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Sphingolipid Metabolism and Signaling
- Mitochondrial Function and Pathology
- S100 Proteins and Annexins
- Lysosomal Storage Disorders Research
- Wnt/β-catenin signaling in development and cancer
- Trace Elements in Health
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Drug Transport and Resistance Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Anesthesia and Neurotoxicity Research
- 14-3-3 protein interactions
- Cancer-related gene regulation
- Advanced Neuroimaging Techniques and Applications
- Traumatic Brain Injury and Neurovascular Disturbances
- Traumatic Brain Injury Research
- Machine Learning in Bioinformatics
- Cholinesterase and Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Protease and Inhibitor Mechanisms
- Nuclear Structure and Function
McGill University
2017-2021
Jewish General Hospital
2017-2021
Université de Poitiers
2010-2017
Université Laval
2014-2017
Centre hospitalier de l'Université Laval
2014-2017
Wilfrid Laurier University
2015-2016
Centre hospitalier universitaire de Québec
2014
Polymères, Biopolymères, Surfaces
2011
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...
Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by polyglutamine expansions in the amino-terminal region of huntingtin (Htt) protein. At cellular level, neuronal death accompanied proteolytic cleavage, misfolding and aggregation huntingtin. Abnormal hyperphosphorylation tau protein a characteristic feature class diseases called tauopathies. As number studies have reported pathology HD patients, we investigated whether may promote if so tackle some its...
Abstract Activated Caspase-6 (Casp6) is associated with age-dependent cognitive impairment and Alzheimer disease (AD). Mice expressing human in hippocampal CA1 neurons develop deficits, neurodegeneration neuroinflammation. This study assessed if methylene blue (MB), a phenothiazine that inhibits caspases, alters Caspase-6-induced mice. Aged cognitively impaired Casp6-overexpressing mice were treated drinking water for 1 month. Methylene treatment did not alter levels, by RT-PCR, western blot...
The activation of the aspartate-specific cysteinyl protease, Caspase-6, is proposed as an early pathogenic event Alzheimer disease (AD) and Huntington's disease. Caspase-6 inhibitors could be useful against these neurodegenerative diseases but most have been exclusively studied in vitro or show acute liver toxicity humans. Here, we assessed vinyl sulfone small molecule peptide caspase for potential use vivo. IC50 NWL were determined on Caspase-1 to 10, Caspase-6-transfected human colon...
Glycogen synthase kinase 3β (GSK3β) activity is regulated by phosphorylation processes and regulates in turn through several proteins, including eukaryotic initiation factor 2B (eIF2B). Serine 9 of GSK3β (pGSK3βSer9), usually promoted activation the PI3K/Akt survival pathway, triggers inhibition. By contrast, tyrosine 216 (pGSK3βTyr216) increases under apoptotic conditions, leading to activation. Lithium chloride (LiCl) described increase pGSK3βSer9 resulting The purpose this study...
There is evidence linking sphingolipid abnormalities, APP processing, and neuronal death in Alzheimer's disease (AD). We previously reported a strong elevation of ceramide levels the brain APP(SL)/PS1Ki mouse model AD, preceding death. To extend these findings, we analyzed related-sphingolipid contents from two other models (i.e., APP(SL) APP(SL)/PS1(M146L)) which time-course pathology closer to that seen most currently available models. Conversely our previous work, ceramides did not...
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...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22789-7
Caspase-6 (Casp6), a cysteinyl protease of the caspase family, is activated early in Huntington disease (HD) and thought to contribute its pathogenesis by generating toxic fragment huntingtin (Htt). Active Casp6 TauΔCasp6 were assessed 50–70 yr old grade II HD age-matched control brains immunohistochemistry with neoepitope antisera against active Tau cleaved (TauΔCasp6). To assess whether activity induces HD-like pathogenesis, transgenic knock-in mouse (ACK) expressing self-activated form...