A5067205297- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Viral Infections and Immunology Research
- Trace Elements in Health
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Genetic Neurodegenerative Diseases
- Glycosylation and Glycoproteins Research
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- biodegradable polymer synthesis and properties
- Protein Structure and Dynamics
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Muscle Physiology and Disorders
- Traumatic Brain Injury and Neurovascular Disturbances
- Nicotinic Acetylcholine Receptors Study
- Hereditary Neurological Disorders
- Animal Disease Management and Epidemiology
- Nerve injury and regeneration
University of British Columbia
2016-2025
Amorfix (Canada)
2013-2024
Vancouver Coastal Health
2010-2020
Vancouver Coastal Health Research Institute
2013-2020
Vancouver General Hospital
2020
GF Strong Rehabilitation Centre
2016-2020
University of British Columbia Hospital
2006-2017
Public Health Agency of Canada
2011-2016
Ottawa Hospital
2014-2016
Spinal Cord Injury BC
2016
We have developed a series of mouse-mouse neural hybrid cell lines by fusing the aminopterin-sensitive neuroblastoma N18TG2 with motor neuron-enriched embryonic day 12–14 spinal cord cells. Of 30 neuroblastoma-spinal (NSC) hybrids displaying multipolar neuron-like phenotype, 10 express choline acetyltransferase, and 4 induce twitching in cocultured mouse myotubules. NSC-19, NSC-34, their subclones additional properties expected neurons, including generation action potentials, expression...
In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption mussels found to be contaminated with domoic acid, which is structurally related excitatory neurotransmitter glutamate. We studied manifestations 14 more severely affected patients assessed neuropathological findings 4 others who died within four months ingesting mussels. acute phase mussel-induced intoxication, had headache, seizures, hemiparesis, ophthalmoplegia, abnormalities...
The “modified host protein” model of scrapie proposes that the transmissible agent is composed degradation-resistant protein, Sp33–37, and clinical pathologic signs result from neurotoxic accumulations this protein. Sp33–37 an abnormal, amyloidogenic isoform normally occurring cellular protein Cp33–37. This study investigated tissue distribution Cp33–37 in hamster. In brain, was most concentrated hippocampal formation. Immunohistochemical studies localized to neurons surrounding neuropil...
The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: TDP-43 proteinopathies. first pathogenic mutations gene encoding (TARDBP) were recently reported familial sporadic ALS patients, supporting direct role for neurodegeneration. In this study, we report identification functional analyses two one...
Significance Amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease, is associated with mutation and misfolding of the Cu/Zn superoxide dismutase (SOD1) protein. Prior studies found that mutant misfolded SOD1 can convert wild-type (WT) to a form inside living cells in prion-like fashion. We now report WT be transmitted from cell cell, propagated protein perpetuated. Misfolded transmission between mediated through release uptake aggregates or via small membrane-bounded...
Human wild-type superoxide dismutase-1 (wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic lateral sclerosis (FALS), double transgenic models of FALS, and cell culture systems, but the structural determinants this process are unclear. Here we molecularly dissect effects intracellular cell-free obligately misfolded proteins on natively structured SOD1. Expression enzymatically inactive, natural ALS mutations G127X G85R human mesenchymal neural lines induces misfolding...
Fas is a cell surface receptor that transduces death signals when cross-linked by agonist antibodies or fas ligand. In this study, we examined the potential of to contribute oligodendrocyte (OL) injury and demyelination as they occur in human demyelinating disease multiple sclerosis (MS). Immunohistochemical study central nervous system (CNS) tissue from MS subjects demonstrated elevated expression on OLs chronic active silent lesions compared with control without other neurologic diseases....
Proteinacious intracellular aggregates in motor neurons are a key feature of both sporadic and familial amyotrophic lateral sclerosis (ALS). These inclusion bodies often immunoreactive for Cu,Zn-superoxide dismutase (SOD1) implicated the pathology ALS. On basis this similar clinical presentation symptoms (fALS) forms ALS, we sought to investigate possibility that there exists common disease-related aggregation pathway fALS-associated mutant SODs wild type SOD1. We have previously shown...
The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal cord motor neurons is a pathological hallmark amyotrophic lateral sclerosis (ALS). Although SOD1 abundant all cells, its half-life far exceeds any other cell type. On the basis premise long protein increases potential for oxidative damage, we investigated effects oxidation on misfolding/aggregation and ALS-associated mutants. Zinc-deficient wild-type mutants were extremely prone to form visible...
Mutations in copper/zinc superoxide dismutase (SOD1) are causative for dominantly inherited amyotrophic lateral sclerosis (ALS). Despite high variability biochemical properties among the disease-causing mutants, a proportion of both dismutase-active and -inactive mutants stably bound to spinal cord mitochondria. This mitochondrial floats with mitochondria rather than sedimenting much higher density protein, thus eliminating coincidental cosedimentation protein aggregates Half ≈90%...
Abstract : X‐linked spinal and bulbar muscular atrophy (SBMA), Kennedy's disease, is a degenerative disease of the motor neurons that associated with an increase in number CAG repeats encoding polyglutamine stretch within androgen receptor (AR). Recent work has demonstrated gene products open reading frame triplet repeat expansions may be substrates for cysteine protease cell death executioners, caspases. However, role caspase cleavage plays cytotoxicity expression disease‐associated alleles...
Abstract We describe the development of temporal lobe epilepsy in an 84‐year‐old man who had suffered domoic acid intoxication. Following intoxication he nausea, vomiting, confusion, and coma. Generalized convulsions complex partial status epilepticus progressively developed. After 3 weeks improved was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions...
Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide cellular signals initiate identify such cytokines, we have tested found supernatants derived subsets activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured adult astrocytes. This effect blocked by neutralizing antibody...
Apoptosis is a fundamental process required for normal development of the nervous system and triggered during neurodegenerative disease. To dissect molecular events leading to neuronal cell death, we have developed cell-free model apoptosis. The faithfully reproduces key elements apoptosis, including chromatin condensation, DNA fragmentation, caspase activation/processing, selective substrate cleavage. We report that apoptosis activated in premitochondrial, mitochondrial, postmitochondrial...
The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted controlled study this syndrome by analyzing clinical, electromyographic, muscle-biopsy features in 18 patients with history poliomyelitis--13 reporting 1 to 20 years weakness 5 without symptoms. also reported muscle atrophy (9 13) fatigue (10 13), symptoms not the controls. age at time poliomyelitis, severity residual disability, number since were comparable...