Garth A. Nicholson
A5077466041- Hereditary Neurological Disorders
- Amyotrophic Lateral Sclerosis Research
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Cellular transport and secretion
- Muscle Physiology and Disorders
- RNA regulation and disease
- Botulinum Toxin and Related Neurological Disorders
- Endoplasmic Reticulum Stress and Disease
- Peripheral Neuropathies and Disorders
- RNA modifications and cancer
- Cellular Mechanics and Interactions
- DNA Repair Mechanisms
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Prion Diseases and Protein Misfolding
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- Myasthenia Gravis and Thymoma
- Neurological disorders and treatments
Concord Repatriation General Hospital
2015-2024
Macquarie University
2015-2024
The University of Sydney
2015-2024
Anzac Research Institute
2015-2024
Emory University
2018-2024
King's College London
2008-2021
Illumina (United States)
2021
Trinity College Dublin
2021
Neuroscience Institute
2021
Polish Academy of Sciences
2005-2020
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system uncertain, and mechanistic role neurodegeneration remains speculative. We identified neighboring mutations highly conserved region TARDBP sporadic familial ALS cases. TARDBPM337V segregated with disease within one kindred genome-wide scan confirmed that linkage was restricted to chromosome...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that familial in 10% of cases. We have identified missense mutation the gene encoding fused sarcoma (FUS) British kindred, linked to ALS6. In survey 197 ALS index cases, we two further mutations eight families. Postmortem analysis three cases with FUS showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization mutant...
Abstract We describe an Australian family of Greek origin with a parkinsonian syndrome and Ala53Thr α‐synuclein gene mutation. Five 9 siblings were affected, the average age onset was 45 years, initial symptoms variable, including resting tremor, bradykinesia, gait disturbance, as previously described in families same point Affected members responded well to levodopa, developed progressive cognitive impairment, had disease duration 5 16 years. Pathologic features typical idiopathic...
Familial amyotrophic lateral sclerosis (FALS) is an inherited neurodegenerative disorder of the motor neurons. While 10–15% cases are caused by mutations in copper/zinc superoxide-dismutase-1 (SOD-1) gene, dying-forward hypothesis, which corticomotoneurons induce anterograde excitotoxic motoneuron degeneration, has been proposed as a potential mechanism. The present study applied novel threshold tracking transcranial magnetic stimulation techniques to investigate mechanisms underlying...
Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS TDP-43, raising the possibility additional might contribute to ALS pathogenesis. We performed systematic survey these find candidates similar followed by bioinformatics predict domains subset...
HSAN1 is an inherited neuropathy found to be associated with several missense mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT). SPT catalyzes condensation and palmitoyl-CoA, initial step de novo synthesis sphingolipids. Here we show that induce a shift substrate specificity SPT, which leads formation two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-sphinganine 1-deoxymethyl-sphinganine. Both metabolites lack C1 hydroxyl group sphinganine can therefore neither converted...
Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system widely considered be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement genetic components.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three share several features, including the presence of bioinformatics-predicted prion domain, aggregation–prone nature vitro vivo toxic effects when expressed multiple model systems. Given these commonalities, we hypothesized that protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also...
Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of TDP-43 is a major component, characteristic pathological feature most ALS FTD patients. Here we use genome-wide linkage analysis large ALS/FTD kindred to identify novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified CCNF missense mutation...
To our knowledge, the efficacy of transferring next-generation sequencing from a research setting to neuromuscular clinics has never been evaluated.To translate whole-exome (WES) clinical practice for genetic diagnosis large cohort patients with limb-girdle muscular dystrophy (LGMD) whom protein-based analyses and targeted Sanger failed identify cause their disorder.We performed WES on 60 families LGMDs (100 exomes). Data analysis was between January 6 December 19, 2014, using xBrowse...
<h3>Objective</h3> <i>FUS</i> gene mutations were recently identified in familial amyotrophic lateral sclerosis (ALS). The present studies sought to define the clinical, post-mortem and neurophysiological phenotypes ALS families with determine frequency of sporadic ALS. <h3>Methods</h3> was screened for cases. Clinical, features large are described. <h3>Results conclusions</h3> evident 3.2% (4/124) ALS, representing second most common abnormality be described after <i>SOD1</i>. No 247...