A5004180672- Trace Elements in Health
- Heavy Metal Exposure and Toxicity
- RNA Research and Splicing
- Ferroptosis and cancer prognosis
- Alzheimer's disease research and treatments
- Iron Metabolism and Disorders
- Selenium in Biological Systems
- RNA regulation and disease
- Aluminum toxicity and tolerance in plants and animals
- Insect Resistance and Genetics
- Cellular transport and secretion
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Adipose Tissue and Metabolism
- Neurological diseases and metabolism
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- Cholinesterase and Neurodegenerative Diseases
- Calpain Protease Function and Regulation
- Regulation of Appetite and Obesity
- Climate Change and Health Impacts
- Diet and metabolism studies
- Viral Infectious Diseases and Gene Expression in Insects
- Insect and Arachnid Ecology and Behavior
- Protein Degradation and Inhibitors
The University of Melbourne
2008-2023
Florey Institute of Neuroscience and Mental Health
2015-2023
In-Q-Tel
2013
Deakin University
2002-2003
Although the neurogenesis-enhancing effects of exercise have been extensively studied, molecular mechanisms underlying this response remain unclear. Here, we propose that is mediated by exercise-induced systemic release antioxidant selenium transport protein, selenoprotein P (SEPP1). Using knockout mouse models, confirmed SEPP1 and its receptor low-density lipoprotein receptor-related protein 8 (LRP8) are required for increase in adult hippocampal neurogenesis. In vivo infusion increased...
Background and Purpose Diacetyl‐bis(4‐methyl‐3‐thiosemicarbazonato)copper II (Cu (atsm)) ameliorates neurodegeneration delays disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Parkinson's (PD), yet the mechanism action remains uncertain. Promising results were recently reported for separate Phase 1 studies ALS patients PD patients. Affected tissue these disorders shares features elevated Fe, low glutathione increased lipid peroxidation consistent with ferroptosis, a...
Abstract Allelic variation to the APOE gene confers greatest genetic risk for sporadic Alzheimer’s disease (AD). Independent of genotype, low abundance apolipoprotein E (apoE), is characteristic AD CSF, and predicts cognitive decline. The mechanisms underlying genotype apoE level risks are uncertain. Recent fluid imaging biomarker studies have revealed an unexpected link between brain iron, which also forecasts progression, possibly through ferroptosis, iron-dependent regulated cell death...
For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD-like syndromes. However, the mechanisms Mn toxicity are still poorly understood. Here, we demonstrate dose- time-dependently blocks protein translation amyloid precursor (APP) heavy-chain Ferritin (H-Ferritin), both iron homeostatic proteins with neuroprotective features. APP H-Ferritin post-transcriptionally regulated by responsive...
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer, with treatment options often constrained due to inherent resistance malignant cells conventional therapy. We investigated impact triggering programmed cell death (PCD) by using BH3 mimetic drugs in human GBM lines. demonstrate that co-targeting pro-survival proteins BCL-XL MCL-1 was more potent at killing six lines compared therapy Temozolomide or bromodomain inhibitor JQ1 vitro. Enhanced observed U251...
Defects in the mammalian Menkes and Wilson copper transporting P-type ATPases cause severe homeostasis disease phenotypes humans. Here, we find that DmATP7, sole Drosophila orthologue of genes, is vital for uptake vivo. Analysis a DmATP7 loss-of-function allele shows essential embryogenesis, early larval development, adult pigmentation probably required from diet. These are analogous to those caused by mutation mouse human suggesting like Menkes, plays at least two roles cellular level:...
Zinc, copper, and iron ions are involved in amyloid-beta (Aβ) deposition stabilization Alzheimer's disease (AD). Consequently, metal binding agents that prevent metal-Aβ interaction lead to the dissolution of Aβ deposits have become well sought therapeutic diagnostic targets. However, direct intervention between diseases abnormalities has been challenging is partially attributed lack a suitable agent determine modify concentration distribution vivo. In search ionophores, we identified...
Copper homoeostasis was investigated in the Drosophila melanogaster S2 cell line to develop an insect model for study of copper regulation. Real-time PCR studies have demonstrated expression cells putative orthologues human Cu regulatory genes involved uptake, transport, sequestration and efflux Cu. mammalian chaperones, ATOX1 (a orthologue yeast ATX1), CCS (copper chaperone superoxide dismutase), COX17 COX17), SCO1 SCO2, did not significantly respond transcriptionally increased levels,...
Abstract Background Allelic variation to the APOE gene confers greatest genetic risk for sporadic Alzheimer’s disease (AD). Independent of genotype, low abundance apolipoprotein E (apoE), is characteristic AD CSF, and predicts cognitive decline. The mechanisms underlying genotype apoE level risks are uncertain. Recent fluid imaging biomarker studies have revealed an unexpected link between brain iron, which also forecasts progression, possibly through ferroptosis, iron‐dependent regulated...
SUMMARY Divalent metal ion transporter 1 (DMT1; also known as SLC11A2) can transport several metals including Fe and Cu in mammalian systems. We set out to determine whether Malvolio (Mvl), the Drosophila melanogasterorthologue of DMT1, Cu. Overexpression Mvlcaused accumulation S2 cultured cells conversely dsRNAi knockdown endogenous Mvl reduced cellular levels. Cell viability under limiting conditions was following knockdown. A homozygous viable loss-of-function mutant(Mvl97f) sensitive...
Dietary copper is essential for multicellular organisms. Copper redox active and required as a cofactor enzymes such the antioxidant Superoxide Dismutase 1 (SOD1). dyshomeostasis has been implicated in Alzheimer's disease. Mutations presenilin genes encoding PS1 PS2 are major causes of early-onset familial efficient uptake mammalian systems. Here we demonstrate conserved role dietary fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown single (PSN) gene lethal....
Copper is essential for aerobic life, but many aspects of its cellular uptake and distribution remain to be fully elucidated. A genome-wide screen copper homeostasis genes in Drosophila melanogaster identified the SNARE gene Syntaxin 5 (Syx5) as playing an important role regulation; flies heterozygous a null mutation Syx5 display increased tolerance high dietary copper. The phenotype shown here due decrease accumulation, mechanism also observed both human cell lines. Studies adult tissue...
Abstract Aim Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant anti‐inflammatory drug, tempol, modify these responses. Methods Following unilateral nephrectomy, we inserted renal arterial catheters laser‐Doppler/oxygen‐sensing probes cortex medulla. Noanesthetized sheep were administered intravenous...
Dysregulated brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signalling is implicated in several neurodegenerative diseases, including Alzheimer's disease. A failure of support may participate mechanisms, such as ferroptosis, which has likewise been this disease class. The current study investigated whether modulators TrkB affect ferroptosis. Cell viability, C11 BODIPY, and cell-free oxidation assays were used to observe the impact modulators, an immunoblot...