A5042751532- Alzheimer's disease research and treatments
- Trace Elements in Health
- Metalloenzymes and iron-sulfur proteins
- Metal complexes synthesis and properties
- Crystallization and Solubility Studies
- Electron Spin Resonance Studies
- Prion Diseases and Protein Misfolding
- X-ray Diffraction in Crystallography
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- Magnetism in coordination complexes
- Lanthanide and Transition Metal Complexes
- Molecular Sensors and Ion Detection
- Protein Structure and Dynamics
- Electrocatalysts for Energy Conversion
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Metal-Catalyzed Oxygenation Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Marine and coastal ecosystems
- Crystallography and molecular interactions
- Supramolecular Self-Assembly in Materials
- Oil Palm Production and Sustainability
- RNA regulation and disease
- Spine and Intervertebral Disc Pathology
The Royal Melbourne Hospital
2017-2023
The University of Melbourne
2013-2023
Inserm
2023
Institut Pasteur
2023
Université Paris Cité
2023
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2015-2020
Newcastle University
2005-2019
Polish Academy of Sciences
2018
Florey Institute of Neuroscience and Mental Health
2014-2016
Monash University
2001-2014
Numerous conflicting models have been proposed regarding the nature of Cu2+ coordination environment amyloid β (Aβ) peptide, causative agent Alzheimer's disease. This study used multifrequency CW-EPR spectroscopy to directly resolve superhyperfine interactions between and ligand nuclei Aβ, thereby avoiding ambiguities associated with introducing point mutations. Using a library Aβ16 analogues site-specific 15N-labeling at Asp1, His6, His13, His14, numerical simulations resonances delineated...
Copper interactions with the β-amyloid peptide (Aβ) are believed to play a role in Alzheimer's disease (AD), particular due production of reactive oxygen species and Cu2+-mediated oligomerization. To understand that copper might these processes, detailed knowledge fundamental Cu2+/Aβ is essential. date, identity ligand(s) involved Cu2+ coordination by Aβ has remained unclear. Here, we have used site-specific 13C 15N labeling conjunction hyperfine sublevel correlation (HYSCORE) spectroscopy...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive and memory impairment. Within the brain, senile plaques, which comprise extracellular deposits of amyloid-β peptide (Aβ), are most common pathological feature AD. A high concentration Cu(2+) found within these also areas under oxidative stress. Laboratory work has shown that in vitro Aβ will react with to induce aggregation production reactive oxygen species. As such, this interaction offers...
Accumulation of the β-amyloid (Aβ) peptide in extracellular senile plaques rich copper and zinc is a defining pathological feature Alzheimer's disease (AD). The Aβ1-x (x=16/28/40/42) peptides have been primary focus Cu(II) binding studies for more than 15 years; however, N-truncated Aβ4-42 major Aβ isoform detected both healthy diseased brains, it contains novel N-terminal FRH sequence. Proteins with His at third position are known to bind avidly, conditional log K values pH 7.4 range...
A family of dinuclear cobalt complexes with bridging bis(dioxolene) ligands derived from 3,3,3′,3′-tetramethyl-1,1′-spirobis(indane-5,5′,6,6′-tetrol) (spiroH4) and ancillary based on tris(2-pyridylmethyl)amine (tpa) has been synthesized characterized. The ligand is redox-active accessible in the (spirocat–cat)4–, (spiroSQ–cat)3–, (spiroSQ–SQ)2– forms, (cat = catecholate, SQ semiquinonate). Variation (Mentpa; n 0–3) by successive methylation 6-position pyridine rings influences redox state...
The interaction of the small (140 amino acid) protein, α-synuclein (αS), with Cu2+ has been proposed to play a role in Parkinson's disease (PD). While some insight from truncated model complexes gained, nature corresponding binding modes full length protein remains comparatively less well characterized. This work examined recombinant human αS using Electron Paramagnetic Resonance (EPR) spectroscopy. Wild type (wt) was shown bind stoichiometric via two N-terminal at physiological pH. An H50N...
Magnetic resonance spectroscopy is one of the most important tools in chemical and bio-medical research. However, sensitivity limitations typically restrict imaging resolution to ~ 10 µm. Here we bring quantum control detection systems demonstrate high-resolution electron spin using properties an array nitrogen-vacancy centres diamond. Our paramagnetic microscope selectively images electronic species by precisely tuning a magnetic field probes into with external target spins. This provides...
Aβ4-42 is a major species of Aβ peptide in the brains both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind Cu(II) with an affinity approximately 3000 times higher than commonly studied Aβ1-42 Aβ1-40 peptides, which are implicated pathogenesis Metallothionein-3, protein considered orchestrate copper zinc metabolism brain provide antioxidant protection, was shown extract from when acting its native Zn7 MT-3 form. This reaction assumed...
The recent Southeast Asian haze crisis has generated intense public scrutiny over the rate, methods and types of landscape change in tropics. Debate centred on environmental impacts large-scale agricultural expansion, particularly associated loss high carbon stock forest forests conservation value. Focusing palm oil—a versatile food crop source bioenergy—this paper analyses national, international corporate policy initiatives order to clarify current future direction oil expansion Malaysia...
The superior Cu(<sc>ii</sc>) affinity of human copper transporter 1 (hCtr1) drives acquisition from serum albumin (HSA).
The apparent affinity of human serum albumin (HSA) for divalent copper has long been the subject great interest, due to its presumed role as major Cu2+ -binding ligand in blood and cerebrospinal fluid. Using a combination electronic absorption, circular dichroism room-temperature electron paramagnetic resonance spectroscopies, together with potentiometric titrations, we competed tripeptide GGH against HSA reveal conditional binding constant log cKCuCu(HSA) =13.02±0.05 at pH 7.4. This...
8-Hydroxyquinolines (8HQ) have found widespread application in chemistry and biology due to their ability complex a range of transition metal ions. The family 2-substituted 8HQs has been proposed for use the treatment Alzheimer's disease (AD). Most notably, therapeutic PBT2 (Prana Biotechnology Ltd.) shown act as an efficient chaperone, disaggregate metal-enriched amyloid plaques comprised Aβ peptide, inhibit Cu/Aβ redox chemistry, reverse AD phenotype transgenic animal models. Yet...
Graphene oxide (GO) possesses unusual electronic and mechanical properties, including the ability to stabilize graphene radicals (GRs). However, controlled generation of GRs remains a challenge for applications requiring large-scale production. In this study, we demonstrate production by UVB irradiation GO solutions. Electron paramagnetic resonance spectroscopy solutions revealed dose-dependent exponential growth in radical as function exposure time. The were air-stable over long period,...
The rise of palm oil as the world's most consumed vegetable has coincided with exponential growth in research activity. Bibliometric analysis outputs reveals a distinct imbalance type being undertaken, notably disproportionate focus on biofuel and engineering topics. Recognising expansion agriculture across tropics increasing awareness environmental, social economic impacts, we seek to re-orient existing agenda towards one that addresses fundamental urgent questions defined by stakeholder...
Biometals have an important role in AD (Alzheimer's disease) and metal ligands been investigated as potential therapeutic agents for treatment of AD. In recent studies the 8HQ (8-hydroxyquinoline) derivative CQ (clioquinol) has shown promising results animal models small clinical trials; however, actual mode action vivo is still being investigated. We previously reported that CQ–metal complexes up-regulated MMP (matrix metalloprotease) activity vitro by activating PI3K (phosphoinositide...
Copper complexes of metal binding domains synthesized amyloid-β peptides – Aβ(1-16) and N-truncated Aβ(4-16) containing a novel N-terminal FRH sequence, as well its shorter mutants were characterized by cyclic voltammetry. The influence the peptide sequence to copper molar ratio on electrochemical properties obtained structures studied discussed. reversibility redox processes in with Aβ(4-x) derivatives was also investigated. results indicate crucial role Tyr10 process complex, including...