A5026565665- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Neurological Disorders and Treatments
- Bone Tissue Engineering Materials
- Neurological diseases and metabolism
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Congenital heart defects research
- Biochemical and Molecular Research
- Prion Diseases and Protein Misfolding
- Genomics and Rare Diseases
- Autophagy in Disease and Therapy
- Pluripotent Stem Cells Research
- Genomic variations and chromosomal abnormalities
- Neurological Disease Mechanisms and Treatments
Université de Montréal
2010-2024
Centre Hospitalier de l’Université de Montréal
2017-2023
Centre Hospitalier Universitaire Sainte-Justine
2010
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. screened libraries compounds in C. elegans, validated hits zebrafish, and tested the most potent molecule mice small clinical trial. identified class neuroleptics that restored motility elegans was pimozide, which blocked T-type Ca2+ channels these stabilized neuromuscular transmission...
The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans zebrafish animal models expressing mutant human (A315T or G348C) (S57Δ R521H) that reflect certain aspects ALS motor neuron degeneration, axonal deficits, progressive paralysis. To explore potential our humanized...
Intronic hexanucleotide repeat expansions in the C9orf72 gene represent most common genetic cause of neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. This expansion decreases expression affected patients, indicating that loss function (LOF) acts as a pathogenic mechanism. Several models using Danio rerio (zebrafish) for depletion have been developed to explore disease mechanisms consequences LOF. However, inconsistencies exist reported phenotypes,...
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder in which the neuromuscular junction progressively degenerates, leading to movement difficulties, paralysis, and eventually death. ALS currently being treated by only two FDA-approved drugs with modest efficacy slowing disease progression. Often, translation of preclinical findings bedside terminates prematurely as evaluation potential therapeutic compounds focuses on single study or animal model. To circumscribe...
Abstract Axonal degeneration is observed in early stages of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). This generally precedes apoptosis and therefore may be a promising therapeutic target. An increasing number genes have been identified to actively regulate axonal regeneration; however, only few potential targets the context diseases. Here we investigate DLK-1, major regeneration pathway its contribution phenotypes Caenorhabditis elegans ALS models....
Oculopharyngeal muscular dystrophy (OPMD) is caused by a small expansion of short polyalanine (polyAla) tract in the poly(A)-binding protein nuclear 1 (PABPN1). Despite monogenic nature OPMD, no treatment currently available. Here we report an RNA replacement strategy that has therapeutic potential cell and C. elegans OPMD models. We develop selective microRNAs (miRNAs) against PABPN1, miRNAs our previously developed hammerhead ribozymes (hhRzs) are capable reducing expression both mRNA...
In 2006, GRN mutations were first linked to frontotemporal dementia (FTD), the leading cause of non-Alzheimer dementias. While much research has been dedicated understanding genetic causes disease, our mechanistic impacts deficiency only recently begun take shape. With no known cure or treatment available for GRN-related FTD, there is a growing need rapidly advance and/or small-molecule therapeutics this disease. This issue complicated by fact that, while lysosomal dysfunction seems be key...
Mutations in the human DNA/RNA binding protein FUS are associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration, including some aggressive juvenile onset forms. Cytoplasmic inclusions of proteins observed various neurodegenerative disorders, such as Huntington's disease or spinocerebellar ataxia, suggesting that proteinopathy may be a key player neurodegeneration. To better understand pathogenic mechanisms FUS, we created single copy transgenic Caenorhabditis...
ABSTRACT Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease resulting in muscle and neurodegeneration, the leading genetic cause of infant death. SMA arises when there are homozygous deletion mutations human SMN1 gene, to decrease corresponding protein. Although expressed across multiple tissue types, much previous research into focused on neuronal aspect disease, overlooking many potential non-neuronal aspects disease. Therefore, we sought address this...
Abstract Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with complex, multifactorial pathophysiology, most commonly manifest as loss of motor neurons. We introduce new mechanism ALS pathogenesis via novel drug-like small molecule series that targets protein disulfide isomerase (PDI) within previously unappreciated transient and energy-dependent multi-protein complex. This drug was found to have activity in cellular models for both familial sporadic ALS, well transgenic...
Amyotrophic Lateral Sclerosis (ALS) is a devastating and progressive neurodegenerative disease with complex, multifactorial pathophysiology, culminating in death of motor neurons. We introduce new mechanism ALS pathogenesis via study novel drug-like small molecule series that targets subset protein disulfide isomerase (PDI) within previously largely unappreciated transient energy-dependent multi-protein complex enriched for proteins the interactome. This drug, found by phenotypic screen, has...
Abstract In several neurodegenerative diseases including Alzheimer’s disease (AD), tau, a microtubule-associated protein (MAP) enriched in the axon, becomes hyperphosphorylated, detaches from microtubules, redistributes to somato-dendritic compartment and self-aggregates. The mechanisms leading neuronal dysfunction death by tau pathology remain be fully elucidated. C. elegans has been successfully used groups ours identify involved neurodegeneration. We generated three strains, one...