A5013182948- Alzheimer's disease research and treatments
- Lipid Membrane Structure and Behavior
- Cholinesterase and Neurodegenerative Diseases
- Trace Elements in Health
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Glycosylation and Glycoproteins Research
- Electron Spin Resonance Studies
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Mosquito-borne diseases and control
- Hemoglobinopathies and Related Disorders
- Malaria Research and Control
- Parkinson's Disease Mechanisms and Treatments
- Erythrocyte Function and Pathophysiology
- Hemoglobin structure and function
- Immunodeficiency and Autoimmune Disorders
- Drug Transport and Resistance Mechanisms
- Protein Interaction Studies and Fluorescence Analysis
- Iron Metabolism and Disorders
- Herpesvirus Infections and Treatments
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Blood disorders and treatments
The University of Melbourne
2004-2016
Florey Institute of Neuroscience and Mental Health
2013-2016
Wuhan Engineering Science & Technology Institute
2015
Mental Health Research Institute
2001-2013
Victoria University
2013
Monash University
1996-2009
Australian Regenerative Medicine Institute
2007-2008
Massachusetts General Hospital
2007
Ambedkar University Delhi
2006
Victoria Park
2003
Amyloid beta peptide (Abeta) is the major constituent of extracellular plaques and perivascular amyloid deposits, pathognomonic neuropathological lesions Alzheimer's disease. Cu(2+) Zn(2+) bind Abeta, inducing aggregation giving rise to reactive oxygen species. These reactions may play a deleterious role in disease state, because high concentrations iron, copper, zinc have been located diseased brains. Here we show that coordination metal ions Abeta same both aqueous solution lipid...
In studies of Alzheimer's disease pathogenesis there is an increasing focus on mechanisms intracellular amyloid-β (Aβ) generation and toxicity. Here we investigated the inhibitory potential 42 amino acid Aβ peptide (Aβ 1-42 ) activity electron transport chain enzyme complexes in human mitochondria. We found that synthetic specifically inhibited terminal complex cytochrome c oxidase (COX) a dose-dependent manner was dependent presence Cu 2+ specific “aging” solution. Maximal COX inhibition...
A major source of free radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. The Alzheimer's disease amyloid precursor protein (APP) is a regulator neuronal copper homeostasis. APP knockout mice elevated levels cerebral cortex, whereas APP-overexpressing transgenic reduced levels. Importantly, binding to can greatly reduce औ vitro. understand this interaction at molecular level we solved structure...
The abnormal form of the prion protein (PrP) is believed to be responsible for transmissible spongiform encephalopathies. A peptide encompassing residues 106−126 human PrP (PrP106−126) neurotoxic in vitro due its adoption an amyloidogenic fibril structure. Alzheimer's disease amyloid β (Aβ) also undergoes fibrillogenesis become neurotoxic. Aβ aggregation and toxicity highly sensitive copper, zinc, or iron ions. We show that PrP106−126 aggregation, as assessed by turbidometry, abolished...
Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles and amyloid plaques, which are abnormal protein deposits. The major constituent plaques neurotoxic beta-amyloid peptide (Abeta); genetics familial AD support a direct role for this in AD. Abeta neurotoxicity linked to hydrogen peroxide formation. coordinates redox active transition metals, copper iron, catalytically generate reactive oxygen species. chemical mechanism underlying process not well defined....
Dopamine (DA) and alpha-synuclein (alpha-SN) are two key molecules associated with Parkinson's disease (PD). We have identified a novel action of DA in the initial phase alpha-SN aggregation demonstrate that induces to form soluble, SDS-resistant oligomers. The DA:alpha-SN oligomeric species not amyloidogenic as they do react thioflavin T lack typical amyloid fibril structures visualized electron microscopy. Circular dichroism studies indicate presence lipid membranes interacts alpha-SN,...
Chemical radiculitis is an inflammatory condition of the nerve root due to rupture annulus fibrosus and dissemination disk fluid along sheath. The component glycoprotein. inflammation a reaction repeated injuries spinal column, as for example, in occupational lifting heavy loads. Rupture liberation into tissues also evokes circulating antibody response auto immune reaction. A high titer glycoprotein at 3 weeks after acute attack back pain evidence presence significant lesion. In selected...
Lipid analyses of the human immunodeficiency virus (HIV) propagated in Hut 78 cells indicated a low total lipid/protein ratio, high cholesterol/phospholipid molar and major phospholipids consisting phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine; comparable lipid profiles were noted for erythrocytes other RNA viruses. Electron spin resonance (ESR) studies HIV labeled with 5-nitroxide stearate (N-oxy-4',4'-dimethyloxazolidine derivative ketostearate) showed...
The interaction of Aβ peptides with the lipid matrix neuronal cell membranes plays an important role in pathogenesis Alzheimer's disease. By using EPR and CD spectroscopy, we found that presence Cu<sup>2+</sup> or Zn<sup>2+</sup>, pH, cholesterol, length peptide chain influenced these bilayers. In Aβ40 Aβ42 both inserted into bilayer over pH range 5.5–7.5, as did Cu<sup>2+</sup>. However, only penetrated at 5.5–6.5; higher there was a change coordination sphere inhibited membrane insertion....
Alzheimer's disease is the leading cause of dementia in elderly. Pathologically it characterized by presence amyloid plaques and neuronal loss within brain tissue affected individuals. It now widely hypothesised that fibrillar structures represent an inert structure. Biophysical toxicity assays attempting to characterize formation both intermediate oligomeric Aβ typically involves preparing samples which are largely monomeric; most common method this achieved use fluorinated organic solvent...
Greater reproductive variance among males than females is presented as a component of natural selection's influence in determining preferential treatment the inheritance wealth. In conjunction, transmission sex chromosomes and their attendant probabilities carrying genes identical by descent are traced for several generations order to illustrate male bias species whose heterogametic (XY) while female homogametic (XX). The effect this on coefficients relationship (direct additive) leads...
The extracellular accumulation of amyloid β (Aβ) peptides is characteristic Alzheimer's disease (AD). However, formation diffusible, oligomeric forms Aβ, both on and off pathways to fibrils, thought include neurotoxic species responsible for synaptic loss neurodegeneration, rather than polymeric aggregates. 8-hydroxyquinolines (8-HQ) clioquinol (CQ) PBT2 were developed their ability inhibit metal-mediated generation reactive oxygen from Aβ:Cu complexes have undergone preclinical Phase II...
The toxicity of the amyloid-β peptide (Aβ) is thought to be responsible for neurodegeneration associated with Alzheimer disease. Generation hydrogen peroxide has been implicated as a key step in toxic pathway. Aβ coordinates redox active metal ion Cu2+ catalytically generate H2O2. Structural studies on interaction Cu have suggested that coordination sphere about resembles site superoxide dismutase 1. To investigate potential role such structures Aβ, two novel Aβ40 peptides, Aβ40(HisτMe) and...
The amyloid beta peptide (Abeta) is toxic to neuronal cells, and it probable that this toxicity responsible for the progressive cognitive decline associated with Alzheimer's disease. However, nature of Abeta species its precise mechanism action remain be determined. It has been reported methionine residue at position 35 a pivotal role play in Abeta. We examined effect mutating valine Abeta42 (AbetaM35V). neurotoxic activity AbetaM35V on primary mouse cortical cells was enhanced, diminished...
Research Article| December 01 1955 The nature of the protein in hyaluronic complex bovine synovial fluid C. Curtain 1Department Biochemistry, University Oxford Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd © CAMBRIDGE UNIVERSITY PRESS1955 Biochem J (1955) 61 (4): 688–697. https://doi.org/10.1042/bj0610688 Views Icon Article contents Figures & tables Video Audio Supplementary Data Peer Review Share...
Crude fluorescein antibody-globulin conjugates may be freed of soluble derivatives and other low-molecular weight by-products by filtration through a Sephadex column G25. Nonspecifically staining conjugate removed the fluorescein-globulin N,N-diethlaminoethyl cellulose in pH 6.0 0.02 M phosphate buffer. The method used for either purifiying fluores antibody or isolating non-specifically components crude conjugates.