A5082082058- Trace Elements in Health
- Alzheimer's disease research and treatments
- Heavy Metal Exposure and Toxicity
- Drug Transport and Resistance Mechanisms
- Cellular transport and secretion
- Electrochemical Analysis and Applications
- RNA Research and Splicing
- Metal complexes synthesis and properties
- Aluminum toxicity and tolerance in plants and animals
- Pharmacological Effects and Toxicity Studies
- Cancer-related Molecular Pathways
- Ferroptosis and cancer prognosis
- Neuroscience and Neuropharmacology Research
- ATP Synthase and ATPases Research
- CRISPR and Genetic Engineering
- Selenium in Biological Systems
- Advanced biosensing and bioanalysis techniques
- Bipolar Disorder and Treatment
- Circular RNAs in diseases
- Autophagy in Disease and Therapy
- Genomics, phytochemicals, and oxidative stress
- RNA Interference and Gene Delivery
- Iron Metabolism and Disorders
- RNA regulation and disease
- Molecular Biology Techniques and Applications
The University of Melbourne
2010-2022
Florey Institute of Neuroscience and Mental Health
2013-2022
Mental Health Australia
2016
Mental Health Research Institute
2006-2012
Deakin University
2008
J. Neurochem. (2011) 119 , 220–230. Abstract Impaired metal ion homeostasis causes synaptic dysfunction and treatments for Alzheimer’s disease (AD) that target ions have therefore been developed. The leading compound in this class of therapeutic, PBT2, improved cognition a clinical trial with AD patients. aim the present study was to examine cellular mechanism action PBT2. We show PBT2 induces inhibitory phosphorylation α‐ β‐isoforms glycogen synthase kinase 3 activity is dependent on...
Abstract Mutations in presenilin 1 and 2 ( PS1 PS2 ) cause autosomal dominant familial Alzheimer’s disease (FAD). Ferroptosis has been implicated as a mechanism of neurodegeneration AD since neocortical iron burden predicts (AD) progression. We found that loss the presenilins dramatically sensitizes multiple cell types to ferroptosis, but not apoptosis. FAD causal mutations similarly cells ferroptosis. The promote expression GPX4, selenoprotein checkpoint enzyme blocks ferroptosis by...
Menkes' disease is a fatal, X-linked, copper deficiency disorder that results from defective efflux intestinal cells and inadequate delivery to other tissues, leading deficiencies of critical copper-dependent enzymes. Wilson's an autosomally inherited, toxicosis resulting biliary excretion copper, which leads accumulation in the liver. The ATP7A ATP7B genes are patients with diseases, respectively, encode transmembrane, P-type ATPase proteins (ATP7A or MNK WND, respectively) function...
The Menkes protein (MNK; ATP7A) functions as a transmembrane copper-translocating P-type ATPase and plays vital role in systemic copper absorption the gut reabsorption kidney. Polarized epithelial cells such Madin-Darby canine kidney (MDCK) are physiologically relevant model for vivo. In this study, cultured MDCK were used to characterize MNK trafficking enabled identification of signaling motifs required target specific membranes. Using confocal laser scanning microscopy surface...
Our expression microarray studies showed messenger RNA (mRNA) for solute carrier family 39 (zinc transporter), member 12 (SLC39A12) was higher in dorsolateral prefrontal cortex from subjects with schizophrenia (Sz) comparison controls. To better understand the significance of these data we ascertained whether SLC39A12 mRNA altered a number cortical regions (Brodmann's area (BA) 8, 9, 44) Sz, BA 9 mood disorders and rats treated antipsychotic drugs. In addition, determined inducing resulted...
MNK (Menkes copper-translocating P-type ATPase, or the Menkes protein; ATP7A) plays a key role in regulating copper homoeostasis humans. has been shown to have dual cell: it delivers cuproenzymes Golgi compartment and effluxes excess from cell. These roles can be achieved through copper-regulated trafficking of MNK. It previously undergo trans-Golgi network plasma membrane response elevated concentrations, endocytosed upon removal copper. However, fundamental question as whether influences...
Copper deficiency during pregnancy results in early embryonic death and foetal structural abnormalities including skeletal, pulmonary cardiovascular defects. During pregnancy, copper is transported from the maternal circulation to foetus by mechanisms which have not been clearly elucidated. Two copper-transporting ATPases, Menkes (ATP7A; MNK) Wilson (ATP7B; WND), are expressed placenta both involved placental transport, as accumulates disease. The regulatory of MNK WND their exact role...
Background/Aims: The copper transporting ATPases, Menkes (ATP7A; MNK) and Wilson (ATP7B; WND) are essential for normal transport in the human body. placenta is key organ supply to fetus during pregnancy it one of few organs body express both ATPases. therefore provides a unique opportunity elucidate specific roles these transporters within cell type. Methods/Results: Using polarized placental Jeg-3 cells, siRNA technology radio-labelled <sup>64</sup>Cu assays, MNK WND were shown have...
A role for the copper transporter, ATP7B, in secretion of from human breast into milk has previously not been reported, although it is known that murine ortholog ATP7B facilitates mouse mammary gland. We show here expressed luminal epithelial cells both resting and lactating breast, where a perinuclear localization diffuse location tissue. protein was present different subset vesicles those containing proteins did overlap with Menkes ATPase, ATP-7A, except region cells. In cultured line,...
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....
SUMMARY Nutrient copper supply is critical for cell growth and differentiation, its disturbance associated with major pathologies including cancer neurodegeneration. Although increasing bioavailability in late Precambrian facilitated emergence of novel cuproproteins, their intricate regulation by this essential trace element remains largely cryptic. We found that subtle rises cellular strikingly increase polyubiquitination accelerate protein degradation within 30 minutes numerous mammalian...
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...
The induced pluripotent stem cell (iPSC) lines UOWi002-A and UOWi003-A were reprogrammed from dermal fibroblasts via mRNA transfection. Dermal a 56 year old female caucasian familial Alzheimer's disease patient carrying A246E mutation in the PSEN1 gene (familial AD3, autopsy confirmed disease) 75 non-demented control same family bearing wild-type A246 genotype obtained Coriell Institute (AG06848 AG06846, respectively). generated iPSCs characterized pluripotency was confirmed. maintained both...
Abstract Neurodegenerative illnesses are characterized by aberrant metabolism of biometals such as copper (Cu), zinc (Zn) and iron (Fe). However, little is known about the metabolic effects associated with altered metal homeostasis. In this study, we used an in vitro model Cu homeostasis to investigate how regulates cellular protein expression. Human fibroblasts containing a natural deletion mutation Menkes (MNK) ATP7A transporter (MNK deleted) were compared overexpressing transfected)....