A5021224139- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Parkinson's Disease Mechanisms and Treatments
- Free Radicals and Antioxidants
- Nanocluster Synthesis and Applications
- Advanced Chemical Sensor Technologies
- Biotin and Related Studies
- Neuroscience and Neuropharmacology Research
- Molecular Sensors and Ion Detection
- Biochemical Acid Research Studies
- Nuclear Receptors and Signaling
- Platelet Disorders and Treatments
- Neurological diseases and metabolism
- X-ray Diffraction in Crystallography
- RNA regulation and disease
- Biological Research and Disease Studies
- Graph theory and applications
- Neurological disorders and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Crystallization and Solubility Studies
- Cell Adhesion Molecules Research
- Prion Diseases and Protein Misfolding
- Protein Kinase Regulation and GTPase Signaling
- Trace Elements in Health
The University of Melbourne
2008-2024
Florey Institute of Neuroscience and Mental Health
2012-2024
Mental Health Research Institute
2008-2013
Monash University
2005
The definitive indicator of Alzheimer's disease (AD) pathology is the profuse accumulation amyloid-ß (Aß) within brain. Various in vitro and cell-based models have been proposed for high throughput drug screening potential therapeutic benefit diseases protein misfolding. Caenorhabditis elegans offers a convenient vivo system examination Aß toxicity complex multicellular organism. Ease culturing short life cycle make this animal model well suited to rapid candidate compounds.We generated new...
Amelyoid-beta peptide (Abeta) is a major causative agent responsible for Alzheimer's disease (AD). Abeta contains high affinity metal binding site that modulates aggregation and toxicity. Therefore, identifying molecules targeting this represents valid therapeutic strategy. To test hypothesis, range of L-PtCl(2) (L = 1,10-phenanthroline derivatives) complexes were examined shown to bind Abeta, inhibit neurotoxicity rescue Abeta-induced synaptotoxicity in mouse hippocampal slices....
The design of small molecules that can target the aggregation Aβ as potential therapeutic agents for Alzheimer's disease is an area study has attracted a lot attention recently. novel ligand methyl 1-butyl-2-pyridyl-benzimidazole carboxylate was prepared synthesis series new iridium(III), ruthenium(II), and platinum(II) 2-pyridyl-benzimidazole complexes. crystal structure half-sandwich iridium(III) complex established by X-ray diffraction. An arrangement two cationic complexes in unit cell...
Brainwash! A platinum complex (see scheme) was developed that could be administered orally and reduce the amyloid burden in brains of transgenic mouse models suffering from Alzheimer's disease. Analyses brain tissues showed treatment with Pt compound led to a 26 % decrease number β-peptide plaques.
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...
Extended X-ray absorption fine structure spectroscopy, mass spectrometry, dynamic light scattering and density functional theory are combined to derive structural models for the interaction of neurotoxicity-ablating platinum-based compounds with amyloid-β peptide.
Size exclusion chromatography with small angle X-ray scattering and ensemble optimisation modelling reveals conformers in random pool of α-synuclein.
The N-truncated β-amyloid (Aβ) isoform Aβ4–x is known to bind Cu2+ via a redox-silent ATCUN motif with conditional Kd = 30 fM at pH 7.4. This study characterizes the interactions and redox activity of Aβx–16 (x 1, 4) 2-[(dimethylamino)-methyl-8-hydroxyquinoline, terdentate 8-hydroxyquinoline (8HQ) Kd(CuL) 35 pM Metal transfer between Cu(Aβ1–16), CuL, CuL2, ternary CuL(NImAβ) was rapid, while corresponding equilibrium L Aβ4–16 occurred slowly metastable intermediate. Both CuL CuL2 were in...
Apoptotic cell death via activation of the caspase family cysteine proteases is a common feature many neurodegenerative diseases including Creutzfeldt−Jakob disease. Molecular imaging protease activities at preclinical stage may provide valuable mechanistic information about pathophysiological pathways involved in disease evolution and response to therapy. In this study, we report synthesis characterization near-infrared (NIR) fluorescent contrast agent capable noninvasively neuronal...
Abstract The Parkinson's disease ( PD )‐causative leucine‐rich repeat kinase 2 LRRK 2) belongs to the Roco family of G‐proteins comprising a Ras‐of‐complex (Roc) domain followed by C‐terminal Roc COR ) in tandem (called Roc‐ domain). Two prokaryotic domains have been characterized as ‘G proteins activated guanine nucleotide‐dependent dimerization’ GAD s), which require dimerization for activation their GTP ase activity and bind nucleotides with relatively low affinities. Additionally,...
Gehirnwäsche! Ein Platin-Komplex (siehe Schema) wurde entwickelt, der oral gegeben werden kann und die Amyloid-Belastung in den Gehirnen transgener Mausmodelle mit Alzheimer-Krankheit reduziert. Analysen von Gehirngewebe zufolge führte Behandlung Pt-Verbindung zu einer 26 %-igen Verminderung Zahl an Amyloid-β-Peptid-Plaques.
A series of compounds based around combining the neuroprotective properties non-competitive N-methyl D-aspartic acid (NMDA) receptor antagonists with antioxidant functionalities have been prepared. The redox chemistry these has evaluated using cyclic voltammetry, and results compared their radical-scavenging obtained from two standard biological assays, inhibition lipid peroxidation (thiobarbituric reacting substances assay) Sapphire colorimetric assay. Results different methods show general...
ABSTRACT Alpha-synuclein (αSyn) aggregates, detected in the biofluids of patients with Parkinson’s disease, have ability to catalyze their own aggregation, leading an increase number and size aggregates. This self-templated amplification is used by newly developed assays diagnose disease turned presence αSyn aggregates into a biomarker disease. It has become evident that can form fibrils slightly different structures, called “strains” or polymorphs, but little known about differential...
α-Synuclein (αSyn) aggregates, detected in the biofluids of patients with Parkinson's disease (PD), have ability to catalyze their own aggregation, leading an increase number and size aggregates. This self-templated amplification is used by newly developed assays diagnose turns presence αSyn aggregates into a biomarker disease. It has become evident that can form fibrils slightly different structures, called "strains" or polymorphs, but little known about differential reactivity diagnostic...
A series of compounds based around combining the neuroprotective properties non-competitive N-methyl D-aspartic acid (NMDA) receptor antagonists with antioxidant functionalities have been prepared. The redox chemistry these has evaluated using cyclic voltammetry, and results compared their radical-scavenging obtained from two standard biological assays, inhibition lipid peroxidation (thiobarbituric reacting substances assay) Sapphire colorimetric assay. Results different methods show general...
The amyloid-β peptide (Aβ) is believed to be the major causative agent responsible for Alzheimer's disease (AD). Aβ contains a high affinity metal binding site which modulates aggregation and toxicity. Therefore, identifying molecules targeting this represents valid therapeutic strategy. To test hypothesis range of L-PtCl2 (L= [1,10]-phenathroline derivatives) complexes were examined in vitro assays testing ability compounds alter biophysical biochemical properties Aβ. We able show that...