DISEASES OF THE AGEING BRAIN

Characterization of brain-derived extracellular vesicle lipids in Alzheimer's disease

Huaqi Su, Yepy H Rustam, Colin L Masters, Enes Makalic, Catriona A McLean, Andrew F Hill, Kevin J Barnham, Gavin E Reid, Laura J Vella

2021-05-01

Lipid dyshomeostasis is associated with the most common form of dementia, Alzheimer's disease (AD). Substantial progress has been ..

Amyloid Precursor Protein Dimerisation Reduces Neurite Outgrowth

Luan Luu, Giuseppe D Ciccotosto, Laura J Vella, Lesley Cheng, Laila C Roisman, Gerhard Multhaup, Andrew F Hill, Lisa-Marie Munter, Roberto Cappai

2019-01-01

The amyloid precursor protein (APP) undergoes extensive metabolism, and its transport and proteolytic processing can be modulated ..

Modulating Protein Phosphatase 2A Rescues Disease Phenotype in Neurodegenerative Tauopathies

Simon McKenzie-Nickson, Jacky Chan, Keyla Perez, Lin W Hung, Lesley Cheng, Amelia Sedjahtera, Lydia Gunawan, Paul A Adlard, David J Hayne, Lachlan E McInnes, Paul S Donnelly, David Finkelstein, Andrew F Hill, Kevin J Barnham

2018-11-01

Alzheimer's disease (AD) is the leading cause of dementia worldwide accounting for around 70% of all cases. There is currently no ..

Ablation of tau causes an olfactory deficit in a murine model of Parkinson's disease

Leah C Beauchamp, Jacky Chan, Lin W Hung, Benjamin S Padman, Laura J Vella, Xiang M Liu, Bradley Coleman, Ashley I Bush, Michael Lazarou, Andrew F Hill, Laura Jacobson, Kevin J Barnham

2018-07-05

Parkinson's disease is diagnosed upon the presentation of motor symptoms, resulting from substantial degeneration of dopaminergic ..

A rigorous method to enrich for exosomes from brain tissue

Laura J Vella, Benjamin J Scicluna, Lesley Cheng, Emma G Bawden, Colin L Masters, Ching-Seng Ang, Nicholas Willamson, Catriona McLean, Kevin J Barnham, Andrew F Hill

2017-07-26

Extracellular vesicles, including exosomes, are released by all cells, including those of the nervous system. Capable of deliverin..

The Copper bis(thiosemicarbazone) Complex Cu-II(atsm) Is Protective Against Cerebral Ischemia Through Modulation of the Inflammatory Milieu

Mikko T Huuskonen, Qing-zhang Tuo, Sanna Loppi, Hiramani Dhungana, Paula Korhonen, Lachlan E McInnes, Paul S Donnelly, Alexandra Grubman, Sara Wojciechowski, Katarina Lejavova, Yuriy Pomeshchik, Laura Periviita, Lotta Kosonen, Martina Giordano, Frederick R Walker, Rong Liu, Ashley I Bush, Jari Koistinaho, Tarja Malm, Anthony R White

2017-04-01

Developing new therapies for stroke is urgently needed, as this disease is the leading cause of death and disability worldwide, an..

Simplified Murine 3D Neuronal Cultures for Investigating Neuronal Activity and Neurodegeneration

Steven J Collins, Cathryn L Haigh

2017-03-01

The ability to model brain tissue in three-dimensions offers new potential for elucidating functional cellular interactions and co..

Analysis of Cellular Prion Protein Endoproteolytic Processing

Victoria Lewis

2017-01-01

Like numerous proteins of various structural and functional classes, the glycosylphosphatidylinositol (GPI)-anchored cellular prio..

Pathogenic mechanisms of prion protein, amyloid-beta and alpha-synuclein misfolding: the prion concept and neurotoxicity of protein oligomers

Cathryn L Ugalde, David I Finkelstein, Victoria A Lawson, Andrew F Hill

2016-10-01

Proteinopathies represent a group of diseases characterized by the unregulated misfolding and aggregation of proteins. Accumulatio..

A 2-Substituted 8-Hydroxyquinoline Stimulates Neural Stem Cell Proliferation by Modulating ROS Signalling

Cathryn L Haigh, Carolin Tumpach, Steven J Collins, Simon C Drew

2016-09-01

Eight-hydroxyquinolines (8HQs) are a class of compounds that have been identified as potential therapeutics for a number of neurod..

Restoration of intestinal function in an MPTP model of Parkinson's Disease

LJ Ellett, LW Hung, R Munckton, NA Sherratt, J Culvenor, A Grubman, JB Furness, AR White, DI Finkelstein, KJ Barnham, VA Lawson

2016-07-29

Patients with Parkinson's disease often experience non-motor symptoms including constipation, which manifest prior to the onset of..

Advances in the Development of Disease-Modifying Treatments for Amyotrophic Lateral Sclerosis

Diane Moujalled, Anthony R White

2016-03-01

Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset, neurodegenerative disease characterized by the degeneration of u..

Gene dysregulation is restored in the Parkinson's disease MPTP neurotoxic mice model upon treatment of the therapeutic drug Cu-II(atsm)

Lesley Cheng, Camelia YJ Quek, Lin W Hung, Robyn A Sharples, Nicki A Sherratt, Kevin J Barnham, Andrew F Hill

2016-03-01

The administration of MPTP selectively targets the dopaminergic system resulting in Parkinsonism-like symptoms and is commonly use..

Prion protein "gamma-cleavage": characterizing a novel endoproteolytic processing event

Victoria Lewis, Vanessa A Johanssen, Peter J Crouch, Genevieve M Klug, Nigel M Hooper, Steven J Collins

2016-02-01

The cellular prion protein (PrP(C)) is a ubiquitously expressed protein of currently unresolved but potentially diverse function. ..

Apolipoprotein C-II Adopts Distinct Structures in Complex with Micellar and Submicellar Forms of the Amyloid-Inhibiting Lipid-Mimetic Dodecylphosphocholine

Timothy M Ryan, Michael DW Griffin, Duncan J McGillivray, Robert B Knott, Kathleen Wood, Colin L Masters, Nigel Kirby, Cyril C Curtain

2016-01-05

The formation of amyloid deposits is a common feature of a broad range of diseases, including atherosclerosis, Alzheimer's disease..

Amyloid-Beta Peptide Aβ3pE-42 Induces Lipid Peroxidation, Membrane Permeabilization and Calcium-Influx in Neurons

A BUSH, AP Gunn, BX Wong, T Johanssen, JC Griffith, CL Masters, KJ Barnham, JA Duce, RA Cherny

2016-01-01

Pyroglutamate-modified amyloid-β (pE-Aβ) is a highly neurotoxic amyloid-β (Aβ) isoform and is enriched in the brains of individual..

Polyalanine expansions drive a shift into alpha-helical clusters without amyloid-fibril formation

Saskia Polling, Angelique R Ormsby, Rebecca J Wood, Kristie Lee, Cheryl Shoubridge, James N Hughes, Paul Q Thomas, Michael DW Griffin, Andrew F Hill, Quill Bowden, Till Boecking, Danny M Hatters

2015-12-01

Polyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to for..

Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment

L Cheng, JD Doecke, RA Sharples, VL Villemagne, CJ Fowler, A Rembach, RN Martins, CC Rowe, SL Macaulay, CL Masters, AF Hill

2015-10-01

There is no consensus for a blood-based test for the early diagnosis of Alzheimer's disease (AD). Expression profiling of small no..

PBT2 inhibits glutamate-induced excitotoxicity in neurons through metal-mediated preconditioning

Timothy Johanssen, Nuttawat Suphantarida, Paul S Donnelly, Xiang M Liu, Steven Petrou, Andrew F Hill, Kevin J Barnham

2015-09-01

Excitotoxicity is the pathological process by which neuronal death occurs as a result of excessive stimulation of receptors at the..

The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses

Cathryn L Haigh, Carolin Tumpach, Simon C Drew, Steven J Collins

2015-08-07

Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments ..

The prion protein regulates beta-amyloid-mediated self-renewal of neural stem cells in vitro

Steven J Collins, Carolin Tumpach, Qiao-Xin Li, Victoria Lewis, Timothy M Ryan, Blaine Roberts, Simon C Drew, Victoria A Lawson, Cathryn L Haigh

2015-04-11

The beta-amyloid (Aβ) peptide and the Aβ-oligomer receptor, prion protein (PrP), both influence neurogenesis. Using in vitro murin..

MEK1 transduces the prion protein N2 fragment antioxidant effects

CL Haigh, AR McGlade, SJ Collins

2015-04-01

The prion protein (PrP(C)) when mis-folded is causally linked with a group of fatal neurodegenerative diseases called transmissibl..

Stabilization of Nontoxic A beta-Oligomers: Insights into the Mechanism of Action of Hydroxyquinolines in Alzheimer's Disease

Timothy M Ryan, Blaine R Roberts, Gawain McColl, Dominic J Hare, Philip A Doble, Qiao-Xin Li, Monica Lind, Anne M Roberts, Haydyn DT Mertens, Nigel Kirby, Chi LL Pham, Mark G Hinds, Paul A Adlard, Kevin J Barnham, Cyril C Curtain, Colin L Masters

2015-02-18

The extracellular accumulation of amyloid β (Aβ) peptides is characteristic of Alzheimer's disease (AD). However, formation of dif..

The N-Terminal Residues 43 to 60 Form the Interface for Dopamine Mediated alpha-Synuclein Dimerisation

Su Ling Leong, Mark G Hinds, Andrea R Connor, David P Smith, Eva Illes-Toth, Chi LL Pham, Kevin J Barnham, Roberto Cappai

2015-02-13

α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature ..

iSRAP - a one-touch research tool for rapid profiling of small RNA-seq data

Camelia Quek, Chol-hee Jung, Shayne A Bellingham, Andrew Lonie, Andrew F Hill

2015-01-01

Small non-coding RNAs have been significantly recognized as the key modulators in many biological processes, and are emerging as p..

Small angle X-ray scattering analysis of Cu2 -induced oligomers of the Alzheimer's amyloid beta peptide

Timothy M Ryan, Nigel Kirby, Haydyn DT Mertens, Blaine Roberts, Kevin J Barnham, Roberto Cappai, Chi Le Lan Pham, Colin L Masters, Cyril C Curtain

2015-01-01

Research into causes of Alzheimer's disease and its treatment has produced a tantalising array of hypotheses about the role of tra..

Neutron Reflectometry Studies Define Prion Protein N-terminal Peptide Membrane Binding

Anton P Le Brun, Cathryn L Haigh, Simon C Drew, Michael James, Martin P Boland, Steven J Collins

2014-11-18

The prion protein (PrP), widely recognized to misfold into the causative agent of the transmissible spongiform encephalopathies, h..

In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease

Victor L Villemagne, Shozo Furumoto, Michelle T Fodero-Tavoletti, Rachel S Mulligan, John Hodges, Ryuichi Harada, Paul Yates, Olivier Piguet, Svetlana Pejoska, Vincent Dore, Kazuhiko Yanai, Colin L Masters, Yukitsuka Kudo, Christopher C Rowe, Nobuyuki Okamura

2014-05-01

PURPOSE: Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A n..

Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease.

Marcus W Brazier, Anthony G Wedd, Steven J Collins

2014-04-21

Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers o..

Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms

Leslie I Grad, Justin J Yerbury, Bradley J Turner, William C Guest, Edward Pokrishevsky, Megan A O'Neill, Anat Yanai, Judith M Silverman, Rafaa Zeineddine, Lisa Corcoran, Janet R Kumita, Leila M Luheshi, Masoud Yousefi, Bradley M Coleman, Andrew F Hill, Steven S Plotkin, Ian R Mackenzie, Neil R Cashman

2014-03-04

Amyotrophic lateral sclerosis (ALS) is predominantly sporadic, but associated with heritable genetic mutations in 5-10% of cases, ..

Pathogenic Mutations within the Hydrophobic Domain of the Prion Protein Lead to the Formation of Protease-Sensitive Prion Species with Increased Lethality

Bradley M Coleman, Christopher F Harrison, Belinda Guo, Colin L Masters, Kevin J Barnham, Victoria A Lawson, Andrew F Hill

2014-03-01

UNLABELLED: Prion diseases are a group of fatal and incurable neurodegenerative diseases affecting both humans and animals. The pr..

Prion Infection Impairs Cholesterol Metabolism in Neuronal Cells

Huanhuan L Cui, Belinda Guo, Benjamin Scicluna, Bradley M Coleman, Victoria A Lawson, Laura Ellett, Peter J Meikle, Michael Bukrinsky, Nigora Mukhamedova, Dmitri Sviridov, Andrew F Hill

2014-01-10

Conversion of prion protein (PrP(C)) into a pathological isoform (PrP(Sc)) during prion infection occurs in lipid rafts and is dep..

Deregulation of biometal homeostasis: the missing link for neuronal ceroid lipofuscinoses?

Alexandra Grubman, Eveliina Pollari, Clare Duncan, Aphrodite Caragounis, Tea Blom, Irene Volitakis, Andrew Wong, Jonathan Cooper, Peter J Crouch, Jari Koistinaho, Anu Jalanko, Anthony R White, Katja M Kanninen

2014-01-01

Neuronal ceroid lipofuscinoses (NCLs), a group of genetically distinct fatal neurodegenerative disorders with no treatment or cure..

X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder

A Grubman, SA James, J James, C Duncan, I Volitakis, JL Hickey, PJ Crouch, PS Donnelly, KM Kanninen, JR Liddell, SL Cotman, MD de Jonge, AR White

2014-01-01

Biometals such as zinc, iron, copper and calcium play key roles in diverse physiological processes in the brain, but can be toxic ..

Unusual Clinical and Molecular-Pathological Profile of Gerstmann-Straussler-Scheinker Disease Associated With a Novel PRNP Mutation (V176G)

Marion Simpson, Vanessa Johanssen, Alison Boyd, Genevieve Klug, Colin L Masters, Qiao-Xin Li, Roger Pamphlett, Catriona McLean, Victoria Lewis, Steven J Collins

2013-09-01

IMPORTANCE: Here we describe the unusual clinical and molecular-neuropathological profile of a case of Gerstmann-Sträussler-Schein..

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

Bow J Tauro, Rommel A Mathias, David W Greening, Shashi K Gopal, Hong Ji, Eugene A Kapp, Bradley M Coleman, Andrew F Hill, Ulrike Kusebauch, Janice L Hallows, David Shteynberg, Robert L Moritz, Hong-Jian Zhu, Richard J Simpson

2013-08-01

Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenic process defined by the loss of epithelial characteristic..

Cytosolic caspases mediate mislocalised SOD2 depletion in an in vitro model of chronic prion infection

Layla Sinclair, Victoria Lewis, Steven J Collins, Cathryn L Haigh

2013-07-01

Oxidative stress as a contributor to neuronal death during prion infection is supported by the fact that various oxidative damage ..

Altered biometal homeostasis is associated with CLN6 mRNA loss in mouse neuronal ceroid lipofuscinosis

Katja M Kanninen, Alexandra Grubman, Aphrodite Caragounis, Clare Duncan, Sarah J Parker, Grace E Lidgerwood, Irene Volitakis, George Ganio, Peter J Crouch, Anthony R White

2013-06-15

Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevale..

Oligomers, fact or artefact? SDS-PAGE induces dimerization of beta-amyloid in human brain samples

Andrew D Watt, Keyla A Perez, Alan Rembach, Nicki A Sherrat, Lin Wai Hung, Timothy Johanssen, Catriona A McLean, Woan Mei Kok, Craig A Hutton, Michelle Fodero-Tavoletti, Colin L Masters, Victor L Villemagne, Kevin J Barnham

2013-04-01

The formation of low-order oligomers of β-amyloid (Aβ) within the brain is widely believed to be a central component of Alzheimer'..

Prion-infected cells regulate the release of exosomes with distinct ultrastructural features

Bradley M Coleman, Eric Hanssen, Victoria A Lawson, Andrew F Hill

2012-10-01

Exosomes are small membrane-bound vesicles released from cells and found in vivo in most biological fluids. Functions reported for..

Microwave Synthesis of Prion Protein Fragments up to 111 Amino Acids in Length Generates Biologically Active Peptides

John A Karas, Martin Boland, Cathryn Haigh, Vanessa Johanssen, Andrew Hill, Kevin Barnham, Steven Collins, Denis Scanlon

2012-01-01

Misfolded conformers of the prion protein are aetiologically implicated in neurodegenerative conditions termed prion diseases (als..