DISEASES OF THE AGEING BRAIN
Grant number: 628946 | Funding period: 2011 - 2015
The Neurodegeneration Program is discovering the basic pathways that cause Alzheimer’s disease and related diseases of the aging brain; from these discoveries the team are finding new methods for early diagnosis and therapeutic interventions which will allow them to determine whether it is possible to delay the onset or improve the way in which the brain copes with these diseases
Related publications (41)
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
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
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
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
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
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
Developing new therapies for stroke is urgently needed, as this disease is the leading cause of death and disability worldwide, an..
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
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
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
Patients with Parkinson's disease often experience non-motor symptoms including constipation, which manifest prior to the onset of..
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
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
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
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
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
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
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
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
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
The beta-amyloid (Aβ) peptide and the Aβ-oligomer receptor, prion protein (PrP), both influence neurogenesis. Using in vitro murin..
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
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
α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature ..
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
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
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
PURPOSE: Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A n..
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
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
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
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
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
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
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
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
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
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
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
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
Misfolded conformers of the prion protein are aetiologically implicated in neurodegenerative conditions termed prion diseases (als..