Research Papers

Aging Cell  2013 DOI: 10.1111/acel.12178  Adlard PA, Sedjahtera A,  Gunawan L, Lisa Bray, Hare D, Lear J, Doble P, Bush AI, Finkelstein DI, Cherny RA. A Novel Approach To Rapidly Prevent Age-Related Cognitive Decline. 

J Hunt Dis, 2012, 1: 211-219. DOI: 10.3233/JHD-120029 Cherny  RA,  Ayton S, Finkelstein DI, Bush  AI, McColl G , Massa SM. PBT2 reduces toxicity in a C.elegans model of polyQ aggregation and extends lifespan, reduces striatal atrophy and improves motor performance in the R6/2 mouse model of Huntington's disease.

Mol Neurodegen. 2012, 7:57. DOI: 10.1186/1750-1326-7-57McColl  G, Roberts BR, Pukala TL, Kenche VB, Roberts CM, Link CD, Ryan TM, Masters CL, Barnham KJ, Bush AI, Cherny RA (2012). Utility of an improved model of amyloid-beta (Aß1-42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer's disease. 

Free Rad Biol Med 2012, 52: 298-302 James SA, Volitakis I, Adlard PA, Duce JA, Masters CL, Cherny RA, Bush AI. Elevated labileCu is associated with oxidative pathology in Alzheimer disease. 

J Neurochem  2011, 119: 220-230 Crouch, PJ, Savva, MS, Hung, LW , Donnelly, PS , Mot, AI , Parker, SJ Greenough, MA , Volitakis, I ,Adlard, PA ,Cherny, RA ,Masters, CL,; Bush, AI , Barnham, KJ, White, AR. The Alzheimer's therapeutic PBT2 promotes amyloid-beta degradation and GSK3 phosphorylation via a metal chaperone activity.

J Biol Chem 2011, 286: 18320-18330. Fox J, Connor T, Stiles M, Kama J, Lu Z, Dorsey K, Liebermann G, Sapp E, Cherny R, Banks M, Volitakis I, DiFigl Mi, Berezovska O, Bush A, Hersch S; Cysteine  oxidation within N-terminal mutant Huntingtin promotes oligomerization and delays clearance of soluble protein.

J Biol. Inorg Chem, 2010; DOI 10.1007/s00775-009-0600-y Crouch PJ, Tew DJ, Du T, Nguyen DN, Caragounis A, Filiz G, Blake RE, Trounce IA, Soon CP, Laughton K, Perez KA, Li QX, Cherny RA, Masters CL, Barnham KJ, White AR.Restored degradation of the Alzheimer's amyloid-beta peptide by targeting amyloid formation. J Neurochem. 2009;108:1198-207 Hung YH, Bush AI and Cherny RA. Copper in the brain and Alzheimer's disease. 

Neurobiology of Aging, 2009; 30: 1069-1077 Dorothea Strozyk; Lenore J Launer; Paul A Adlard; Robert  A Cherny; Andrew Tsatsanis; Irene Volitakis; Kaj Blennow; Helen Petrovitch, Lon R White, Ashley I. Bush Zinc and copper modulate Alzheimer Aβ levels in human cerebrospinal fluid.  

Lancet Neurology July 29, 2008 DOI:10.1016/S1474-442(08)70167-4
Lars Lannfelt, Kaj Blennow, Henrik Zetterberg, Stellan Batsman, David Ames, John Harrison, Colin L. Masters, Steve Targum, Ashley I. Bush, Ross Murdoch, Janet Wilson, Craig W. Ritchie on behalf of the PBT2-201-EURO study group
Safety, efficacy and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial.

Neuron (2008), doi:10.1016/j.neuron.2008.06.018
Paul A. Adlard, Robert A. Cherny, David I Finkelstein, Elisabeth Gautier, Penny Huggins, Jack Parsons, Elysia Robb, Mikhalina Cortes, Irene Volitakis, Xiang Liu, Jeffrey P. Smith, Keyla Perez, Katrina Laughton, Qiao-Xin Li, Susan A. Charman, Joseph A. Nicolazzo, Simon Wilkins, Karolina Deleva, Toni Lynch, Gaik Kok, Craig W. Ritchie, Rudolph E. Tanzi, Roberto Cappai, Colin L. Masters, Kevin J. Barnham and Ashley I. Bush
Rapid Restoration of Cognition in Alzheimer's Transgenic Mice with 8-Hydroxy Quinoline Analogs is Associated with Decreased Interstitial Aβ

PNAS 2008, vol 105, no. 19, 6813-6818
Kevin J. Barnham, Vijaya B. Kenche, Giuseppe D. Ciccotosto, David P. Smith, Deborah J. Tew, Xiang Liu, Keyla Perez, Greg A. Cranston, Timothy J. Johanssen, Irene Volitakis, Ashley I. Bush, Colin L. Masters, Anthony R. White, Jeffrey P. Smith, Robert A. Cherny, and Roberto Cappai.
Platinum-based inhibitors of amyloid-β as therapeutic agents for Alzheimer's Disease.

FEBS Journal 274 (2007) 3775-3783
Peter J. Crouch, Anthony R. White and Ashley I. Bush
The modulation of metal bio-availability as a therapeutic strategy for the treatment of Alzheimer's disease.

PLOS One In Press
Melov S, Adlard PA, Morten K, Golden TR, Hinerfeld D, Mavros C, Masters CL, Volitakis I, Li Q-X, Laughton K, Hubbard A, Cherny RA, Bush AI.
Mitochondrial Oxidative Stress Causes Hyperphosphorylation of Tau.

Free Radical Biology in Medicine 2007; 42 1534-1542
Watanabe S, Nagano S, Duce J, Kiaei M, Li Q-X, Tucker SM, Tiwari A, Brown RJ, Beal MF, Hayward LJ, Culotta VC, Yoshihara S, Sakoda S, Bush AI.
Increased Affinity For Copper Mediated By Cystein 111 In Forms Of Mutant Superoxide Dismutase 1 Linked To Amyotrophic Lateral Sclerosis.

PLOS One 2007:2, e334
Fox JH, Kama JK, Lieberman G, Chopra R, Dorsey K, Chopra V, Volitakis I, Cherny RA, Bush AI, Hersch SM.
Mechanisms of Copper Ion Mediated Huntington's Disease Progression. Neurobiology of Aging

2007 28: 907-913
Kaur D, Peng J, Chinta S, Rajagopalan S, Di Monte DA, Cherny RA, Andersen JK.
Increased Murine Neonatal Iron Intake Results in Parkinson-like Neurodegeneration with Age. Protein Pept Lett.

2007 14:83-86
Caine J, Volitakis I, Cherny R, Varghese J, Macreadie I.
Abeta Produced as a Fusion to Maltose Binding Protein Can Be Readily Purified and Stably Associayes With Copper and Zinc.

Neurology 2006 67(1)
Religa D, Strozyk D, Cherny RA, Volitakis I, Haroutunian V, Winblad B, Naslund J, Bush AI.
Elevated Cotical Zinc in Alzheimer's Disease.

J. Inorg Biochem 2006 100:952-962
Maynard CJ, Cappai R, Volitakis I, Cherny RA, Masters CL, Li QX, Bush AI.
Gender and Genetic Background Effects on Brain Metals Homeostasis in APP Transgenic and Normal Mice: Implications for Alzheimer's Beta-amyloid Pathology.

J. Biol. Chem 2006 281:17670-17680
White AR, Du T, Laughton KM, Volitakis I, Sharples RA, Hoke DE, Holsinger RMD, Evin G, Cherny RA, Hill AF, Barnham KJ, Li Q_X, Bush AI, Masters CL.
Degradation of the Alzheimer's Disease Amyloid Beta Peptide by Metal-dependent Up-regulation of Metallprotease Activity.

Brain Res 2006 1:31-46
Kaur D, Rajagopalan S, Chinta S, Kumar MJ, Monte D, Cherny RA, Andersen JK
Chronic Ferritin Expression Within Murine Dopaminergic Midbrain Neurons Results in a Progressive Age-Related Neurodegeneration.

Free Rad. Res 2006 40:1-9
Ali FE, Leung A, Cherny RA, Mavros C, Barnham KJ, Separovic F, Barrow CJ.
Dimerisation of N-acetyl-L-tyrosine Ethyl Ester and A Beta Peptides Via Formation of Dityrosine.

Aging Cell 2006 5:69-79
Opazo C, Luza S, Villemagne VL, Volitakis I, Rowe C, Barnham KJ, Strozyk D, Masters CL, Cherny RA, Bush AI.
Radioiodinated Clioquinol as a Biomarker for Beta-amyloid:Zn2+ Complexes in Alzheimer's Disease

Journal of Inorganic Biochemistry 2005: 99, 2403-22
Haeffner F, Smith DG, Barnham KJ, Bush AI.
Model Studies of Cholsterol and Ascorbate Oxidation by Copper Complexes: Relevance to Alzheimer's Disease Beta-amyloid Metallochemistry.

Free Radical Biology in Medicine 2005: 38, 258-61 Melov S, Wolf N, Strozyk D, Doctrow SR, Bush AI.
Mice Transgenic for Alzheimer's Disease Beta-amyloid Develop Lens Cataracts That Are Resued by Antioxidant Treatment

J. Peptide Sci 2005 11: 353-360
Ali FE, Separovic F, Barrow CJ, Cherny RA, Fraser F, Bush AI, Masters CL, Barnham KJ,
Methionine Regulates Copper/Hydrogen Peroxide Oxidation Products of A Beta

J Biol Chem 2005 280:13355-13363
Tickler AK, Smith DG, Ciccotosto GD, Tew DJ, Curtain CC, Carrington D, Masters CL, Bush AI, Cherny RA, Cappai R, Wade JD, Barnham KJ.
Methylation of the Imidazole Side Chains of the Alzheimer Disease Amyloid-beta Peptide Results in Abolition of Superoxide Dismutaselike Structures and Inhibition of Neurotoxicity.

FASEB J 2005 19:1377-9
Cappai R, Leck SL, Tew DJ, Williamson NA, Smith DP, Galatis D, Sharples RA, Curtain CC. Ali FE, Cherny RA, Culvenor JG, Bottomley SP, Masters CL, Barnham KJ, Hill AF.
Dopamine Promotes Alpha-Synuclein Aggregation into SDS-resistant Soluble Oligimers Via a Distinct Folding Pathway

J Clin Invest 2005: 2556-2563
Puglielli L, Friedlich AL, Setchell KDL, Nagano S, Opazo C, Cherny RA, Barnham KJ, Wade JD, Melov S, Kovacs DM, Bush AI.
Cholesterol Oxidase Mimetic Activity of Alzheimer's Disease Beta-Amyloid.

J Biol Chem 2004: 279:51958-51964
Treiber C, Simons A, Strauss M, Hafner M, Cappai R, Bayer T, Multhaup G.
Clioquinol Mediates Copper Uptake and Counteracts Copper Efflux Activities of the Amyloid Precursor Protein of Alzheimer's Disease

J Biol Chem 2004;279:14673-14678
Nagano S, Huang X, Moir RD, Payton SM, Tanzi RE, Bush AI
Peroxidase Activity of Cyclooxygenase-2 (COX-2) Cross-links B-Amyloid (AB) and Generates AB-COX-2 Hetero-oligimers That Are Increased in Alzheimer's Disease

J Biol Chem 2004;279:8602-8607.
Lee J, Kim J, Hong SH, Lee JY, Cherny RA, Bush AI, Palmiter RD, Koh J.
Estrogen Decreases Zinc Transporter 3 Expression and Synaptic Vesicle Zinc Levels in Mouse Brain J Neuroscience

Friedlich AL, Lee J, Groen T, Cherny RA, Volitakis I, Cole TB, Palmiter RD, Koh J, Bush AI.
Neuronal Zinc Exchange with the Blood Vessel Wall Promotes Cerebral Amyloid Angiopathy in an Animal Model of Alzheimer's Disease.

Nat Rev Drug Discov 2004; 3: 205-214.
Barnham KJ, Masters CL, Bush AI.
Neurodegenerative diseases and oxidative stress.

FASEB J and FJ Express 2004; 18:1427-1429 (published online
Barnham KJ, Haeffner F, Ciccotosto GD, Curtain CC, Tew D, Mavros C, Beyreuther K, Ca
Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease B-amyloid.

J Peptide Sci 2004; 10: 210-217.
Yao S, Cherny RA, Bush AI, Masters CL, Barnham KJ.
Characterizing bathocuprioine self-association and subsequent binding to Alzheimer’s disease amyloid B-peptide by NMR.

J Biol Inorg Chem 2004; 9:269-280.
White AR, Barnham KJ, Huang X, Volitakis I, Beyreuther K, Masters CL, Cherny RA, Bush AI, Cappai R.
Iron inhibits neurotoxicity induced by trace copper and biological reductants.

New Generation Vaccines. New York: Marcel Dekker. 3rd edition. 2004, Chapter 81, 997-1002.
Robins-Browne RM, Strugnell RA, Masters CL.
Vaccines against Alzheimer’s disease.

Drug Design Reviews – Online 2004; 1: 75-82.
Barnham KJ, Cherny RA, Cappai R, Melov S, Masters CL, Bush AI.
Metal-protein attenuating compounds (MPACs) for the treatment of Alzheimer’s disease.

Curr Med Chem – Immun Endoc & Metab Agents. 2003; 3: 9-13.
Cherny RA, Masters CL, Bush AI.
The medicinal metallochemistry of Alzheimer’s disease.

Lancet 2003; 361: 1258-1265
Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, Mavros C, Coccia JA, Faget KY, Fitch KA, Masters CL, Tanzi RE, Chylack LT Jr, Bush AI.
Cytosolic B-amyloid deposition and supranuclear cataracts in lenses from people with Alzehimer’s disease.

J Biol Chem 2003;278:17401-17407
Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, Williamson NA, White AR, Hinds MG, Norton RS, Beyreuther K, Masters CL, Parker MW, Cappai R.
Structure of the Alzheimer’s disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis.

J Membrane Biol 2003; 193: 35-45
Kourie JI, Kenna BL, Tew D, Jobling MF, Curtain CC, Masters CL, Barnham KJ, Cappai R.
Copper modulation of ion channels of PrP[106-126] mutant prion peptide fragments.

Proc Nat Acad Sci 2003; 100:11193-11194
Bush AI, Masters CL, Tanzi RE.
Copper, B-amyloid and Alzheimer’s disease: tapping a sensitive connection.

J Biol Chem 2003; 278: 42959-42965
Barnham KJ, Ciccotosto GD, Tickler AK, Ali FE, Smith DG, Williamson NA, Lam Y-H, Carrington D, Tew D, Kocak G, Volitakis I, Separovic F, Barrow CJ, Wade JD,
Maste Neurotoxic, redox-competent Alzheimer’s B-amyloid is released from lipid membrane by methionine oxidation.

J Biol Chem 2003; 278:2977-2982
Curtain CC, Ali FE, Smith DG, Bush AI, Masters CL, Barnham KJ.
Metal ions, pH and cholesterol regulate the interactions of Alzheimer’s disease amyloid-B peptide with membrane lipid.

J Biol Chem 2003; 278:2977-2982. Arch Neurol. 2003;60:1685-1691
Craig W. Ritchie; Ashley I. Bush; Andrew Mackinnon; Steve Macfarlane; Maree Mastwyk; Lachlan MacGregor; Lyn Kiers; Robert Cherny; Qiao-Xin Li; Amanda Tammer; Darryl C
Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting A Amyloid Deposition and Toxicity in Alzheimer Disease: A Pilot Phase 2 Clinical Trial

Arch. Neurol. 2003; 60:1678
Editorial Comment from the Archives of Neurology

J Neuroscience 2002;22:365-376
White AR, Multhaup G, Galatis D, McKinstry WJ, Parker MW, Pipkorn Beyreuther K, Masters CL, Cappai R.
Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer’s disease amyloid precursor protein.

Neuron 2001;30:665-676
Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim YS, Huang X, Goldstein LE, Moir RD, Lim JT, Beyreuther K, Zheng H,
Tan Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits ß-Amyloid Accumulation in Alzheimer’s Disease Transgenic Mice.

Am J Physiol Cell Physiol 2003; 285:C873-C880.
Bahadi R, Farrelly PV, Kenna BL, Curtain CC, Masters CL, Cappai R, Barnham KJ, Kourie JI.
Cu2+-induced modification of the kinetics of AB[1-42] channels.

Neurology 2001;56:1533-1538
Collie A, Maruff P, Shafiq-Antonacci R, Smith M, Hallup M, Schofield PR, Masters CL, Currie J.
Memory decline in healthy older people: Implications for identifying mild cognitive impairment.

J Biol Chem 2001;276:20466-20473
Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Masters CL, Bush AI, Barnham KJ.
Alzheimer’s Disease Amyloid-ß Binds Copper and Zinc to Generate an Allosterically Ordered Membrane-penetrating Structure Containing Superoxide Dismutase-like Subunits.

Biochem 2001;40:8073-8084
Jobling MF, Huang X, Stewart LR, Barnham KJ, Curtain C, Volitakis I, Perugini M, White AR, Cherny RA, Masters CL, Barrow CJ, Collins SJ, Bush AI, Cappai R.
Copper and zinc binding modulates the aggregation and neurotoxic properties of the prion peptide PrP106-126.

J Neurochem 2001;76:1509-1520
White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, Masters CL, Bush AI, Cappai R.
Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer’s-type neurodegnerative pathways.

J Biol Chem 2000;275:19439-19442
Cuajungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT, Atwood CS, Huang X, Farrag YW, Perry G, Bush AI.
Evidence that the ß-Amyloid Plaques of Alzheimer’s Disease Represent the Redox-silencing and Entombment of Aß by Zinc.

J Struct Biol 2000;130:209-216
Cherny RA, Barnham K, Lynch T, Volitakis I, Li Q-X, McLean CA, Multhaup G, Beyruether K, Tanzi RE, Masters CL, Bush AI.
Chelation and intercalation: complementary properties in a compound for the tretment of Alzheimer’s disease.

J Biol Chem 1999;274:37111-37116
Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD,
Glabe Cu(II) Potentiation of Alzheimer Aß Neurotoxicity.

Biochem 1999;38:7609-7616
Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, Cuajungco MP, Gray DN, Lim J, Moir RD, Tanzi RE, Bush AI
The aBeta peptide of Alzheimers Disease directly products hydrogen peroxide through metal ion reduction.