A5068230802- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Neurogenetic and Muscular Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- DNA Repair Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Xenotransplantation and immune response
- RNA Interference and Gene Delivery
- Spinal Cord Injury Research
- T-cell and B-cell Immunology
La Trobe University
2015-2024
Macquarie University
2014-2023
The University of Melbourne
2005-2020
Florey Institute of Neuroscience and Mental Health
2004-2020
Monash Health
2020
Japan External Trade Organization
2008
Ninewells Hospital
1996-2005
University of Dundee
1996-2005
St. Vincent's Hospital
1997
St Vincent's Hospital
1997
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, on this topic has continued to accelerate, and many new scientists have entered field. Our knowledge base relevant technologies also been expanding. Accordingly, it is important update these monitoring autophagy different organisms. Various reviews described range assays that used purpose. Nevertheless, there continues be confusion regarding acceptable methods measure autophagy, especially...
Intronic expansion of a hexanucleotide GGGGCC repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene is major cause familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. However, cellular function C9ORF72 protein remains unknown. Here, we demonstrate that regulates endosomal trafficking. colocalized with Rab proteins implicated autophagy endocytic transport: Rab1, Rab5, Rab7 Rab11 neuronal cell lines, primary cortical neurons human spinal cord motor neurons,...
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...
Microglial NLRP3 inflammasome activation is emerging as a key contributor to neuroinflammation during neurodegeneration. Pathogenic protein aggregates such β-amyloid and α-synuclein trigger microglial activation, leading caspase-1 IL-1β secretion. Both contribute disease progression in the mouse SOD1G93A model of amyotrophic lateral sclerosis (ALS), suggesting role for NLRP3. Prior studies, however, suggested mice microglia do not express NLRP3, generated independent Here, we demonstrate...
Mutations in Cu/Zn superoxide dismutase (SOD1) are linked to motor neuron death familial amyotrophic lateral sclerosis (ALS) by an unclear mechanism, although misfolded SOD1 aggregates commonly associated with disease. Proteomic analysis of the transgenic SOD1G93A ALS rat model revealed significant up-regulation endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI) family members lumbar spinal cords. Expression mutants (mSOD1) led PDI neuron-like NSC-34 cells but not other...
Mutations in the intracellular metalloenzyme superoxide dismutase 1 (SOD1) are linked to neurotoxicity familial amyotrophic lateral sclerosis (ALS) by an unclear mechanism. Golgi fragmentation and endoplasmic reticulum stress early hallmarks of spinal motor neuron pathology transgenic mice overexpressing mutant SOD1, suggesting that dysfunction neuronal secretory pathway may contribute ALS pathogenesis. We therefore proposed SOD1 directly engages modulates based on recent evidence secretion...
Amyotrophic lateral sclerosis is a rapidly progressing fatal neurodegenerative disease characterized by the presence of protein inclusions within affected motor neurons. Endoplasmic reticulum stress leading to apoptosis was recently recognized be an important process in pathogenesis sporadic human amyotrophic as well transgenic models mutant superoxide dismutase 1-linked familial sclerosis. occurs early disease, indicating critical role pathogenesis, and involves upregulation endoplasmic...
In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons glia, where it associates with stress granules (SGs) forms large inclusions. SGs form response to cellular stress, including endoplasmic reticulum (ER) which is induced both familial sporadic ALS. Here we demonstrate that pharmacological induction ER causes TDP-43 accumulate cytoplasm, also SGs. Furthermore, treatment salubrinal,...
Abstract Complement activation products are elevated in the cerebrospinal fluid and spinal cord of patients with amyotrophic lateral sclerosis (ALS). In this study, we demonstrate complement system involvement a rodent model ALS (human SOD1G93A transgenic rats). With end-stage disease, rats displayed marked deposition C3/C3b, significant up-regulation C5aR lumbar cord. This was associated increased numbers C5aR-positive astrocytes. However, expression C5L2, alternative receptor for C5a,...
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease affecting motor neurons. Hexanucleotide (GGGGCC) repeat expansions in non-coding region of C9orf72 are the major cause familial ALS and frontotemporal dementia (FTD) worldwide. The expansion undergoes repeat-associated non-ATG (RAN) translation to produce five dipeptide proteins (DRPs), including poly(GR) poly(PR). Whilst it remains unclear how mutations lead neurodegeneration ALS/FTD, dysfunction...
Fused in sarcoma (FUS) is mutated both sporadic amyotrophic lateral sclerosis (ALS) and familial ALS patients. The mechanisms underlying neurodegeneration are not fully understood, but FUS redistributes from the nucleus to cytoplasm affected motor neurons, where it triggers endoplasmic reticulum (ER) stress. Ataxin-2 a polyglutamine protein which normally contains 22 repeats, expanded repeats (>34) found Spinocerebellar Ataxia type 2. Recently ataxin-2 with intermediate length (27–33) was...
Abstract Background Pathological forms of TAR DNA-binding protein 43 (TDP-43) are present in motor neurons almost all amyotrophic lateral sclerosis (ALS) patients, and mutations TDP-43 also ALS. Loss gain functions implicated pathogenesis, but the mechanisms unclear. While RNA have been widely investigated, its DNA binding roles remain However, recent studies a role for damage response. Methods We used NSC-34 neuron-like cells primary cortical expressing wildtype or ALS associated mutants...
Abstract Frontotemporal dementia and amyotrophic lateral sclerosis are clinically pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.2 genome-wide significant linkage in large European Australian family autosomal dominant inheritance of frontotemporal no mutation known or genes. Here we demonstrate the segregation novel missense variant CYLD (c.2155A>G, p.M719V) within region as cause this family....
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, spinal cord. Unfortunately, there are few effective treatments, thus remains critical need to find novel interventions that can mitigate against its effects. Whilst aetiology of ALS unclear, ageing major risk factor. Ageing slowly progressive process marked by functional decline an organism over lifespan. However, it unclear how...