A5021982269- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- PI3K/AKT/mTOR signaling in cancer
- Cholinesterase and Neurodegenerative Diseases
- Histone Deacetylase Inhibitors Research
- Stress Responses and Cortisol
- Alzheimer's disease research and treatments
- Muscle Physiology and Disorders
- Protein Kinase Regulation and GTPase Signaling
- Endoplasmic Reticulum Stress and Disease
- Biochemical Acid Research Studies
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Prion Diseases and Protein Misfolding
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
- Cancer-related gene regulation
- Sulfur-Based Synthesis Techniques
- Mechanisms of cancer metastasis
- Tryptophan and brain disorders
- CRISPR and Genetic Engineering
Université Laval
2014-2024
Centres Intégré Universitaires de Santé et de Services Sociaux
2022
Centre intégré universitaire de santé et de services sociaux de la Capitale-Nationale
2022
Institut Universitaire en Santé Mentale de Québec
2014
The University of Texas Southwestern Medical Center
2009-2014
Society for Neuroscience
2011
University of Saskatchewan
2007-2009
TAR DNA-binding protein 43 (TDP-43) is associated with a spectrum of neurodegenerative diseases. Although TDP-43 resembles heterogeneous nuclear ribonucleoproteins, its RNA targets and physiological partners remain unknown. Here we identify from cortical neurons by immunoprecipitation followed deep sequencing (RIP-seq). The canonical binding site (TG)n 55.1-fold enriched, moreover, variant adenine in the middle, (TG)nTA(TG)m, highly abundant among reads our RIP-seq library. can be divided...
TDP-43, or TAR DNA-binding protein 43, is a pathological marker of spectrum neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 an RNA/DNA-binding implicated in transcriptional posttranscriptional regulation. Recent work also suggests that associates cytoplasmic stress granules, which are transient structures form response to stress. In this study, we establish sorbitol as novel physiological...
Progranulin (GRN) haploinsufficiency is a frequent cause of familial frontotemporal dementia, currently untreatable progressive neurodegenerative disease. By chemical library screening, we identified suberoylanilide hydroxamic acid (SAHA), Food and Drug Administration-approved histone deacetylase inhibitor, as an enhancer GRN expression. SAHA dose-dependently increased mRNA protein levels in cultured cells restored near-normal expression haploinsufficient from human subjects. Although...
Significance Both overexpression of wild-type fused in sarcoma (FUS) protein and missense mutations can be pathogenic a group related neurodegenerative disorders that includes amyotrophic lateral sclerosis frontotemporal lobar degeneration. It is unclear how FUS cause disease human patients. In this work, we generated novel transgenic mouse models expressing low levels mutant FUS, both which recapitulate aspects the diseases. We found profound difference underlying mechanisms by mutation...
Frontotemporal dementia (FTD) is the most common cause of in people under 60 yr age and pathologically associated with mislocalization TAR DNA/RNA binding protein 43 (TDP-43) approximately half cases (FLTD-TDP). Mutations gene encoding progranulin (GRN), which lead to reduced levels, are a significant familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 neurodegeneration. Here, we report retinal thinning early disease phenotype humans GRN mutations that...
The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)–linked RNA-binding protein called FUS (fused in sarcoma) has been implicated several aspects of RNA regulation, including mRNA translation. mechanism by which affects the translation polyribosomes not established. Here we show that can associate with stalled this association is sensitive to mTOR (mammalian target rapamycin) kinase activity. Specifically, increased Torin1 treatment or when cells are cultured...
Protein misfolding and mislocalization are common themes in neurodegenerative disorders, including the motor neuron disease, amyotrophic lateral sclerosis (ALS). Maintaining proteostasis is a crosscutting therapeutic target, upregulation of heat shock proteins (HSP) to increase chaperoning capacity. Motor neurons have high threshold for upregulating stress inducible HSPA1A, but constitutively express levels HSPA8. This study compared expression these HSPs cultured expressing three variants...
Abstract Altered microRNA (miRNA) expression is a common feature of Huntington’s disease (HD) and could participate in onset progression. However, little known about the underlying causes miRNA disruption HD. We others have previously shown that mutant Huntingtin binds to Ago2, central component biogenesis, disrupts mature levels. In this study, we sought determine if maturation per se was compromised Towards end, characterized major biogenesis pathway components products (pri-miRNA,...
GATOR1 (GAP Activity TOward Rag 1) is an evolutionarily conserved GTPase-activating protein complex that controls the activity of mTORC1 (mammalian Target Of Rapamycin Complex in response to amino acid availability cells. Genetic mutations subunits, NPRL2 (nitrogen permease regulator-like 2), NPRL3 3), and DEPDC5 (DEP domain containing 5), have been associated with epilepsy humans; however, specific effects these on function regulation are not well understood. Herein, we report...
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative diseases that belong to a common disease spectrum based on overlapping clinical, pathological genetic evidence. Early changes the morphology synapses of affected neuron populations in ALS/FTD suggest underlying mechanism requires further investigation. Fused sarcoma (FUS) is DNA/RNA-binding protein with known links ALS/FTD. Expression ALS-linked FUS mutants mice causes cognitive motor defects,...
<h3>Abstract</h3> Genetic mutations in nitrogen permease regulator-like 2 (NPRL2) are associated with a wide spectrum of familial focal epilepsies, autism, and sudden unexpected death epileptics (SUDEP), but the mechanisms by which NPRL2 contributes to these effects not well known. is requisite subunit GAP activity toward Rags 1 (GATOR1) complex, functions as negative regulator mammalian target rapamycin complex (mTORC1) kinase when intracellular amino acids low. Here, we show that loss...
Abstract Frontotemporal dementia (FTD) is a heterogeneous clinical disorder characterized by progressive abnormalities in behavior, executive functions, personality, language and/or motricity. A neuropathological subtype of FTD, frontotemporal lobar degeneration (FTLD)-FET, protein aggregates consisting the RNA-binding fused sarcoma (FUS). The cause FTLD-FET not well understood and there lack genetic evidence to aid investigation mechanisms disease. goal this study was identify variants...
VOLUME 285 (2010) PAGES 6826–6834 PAGE 6829: In the left column (last line), correct sequence of primer-b is 5-GTGGAGGAAACCGGCAGTGCGGTAC-3.