Research Topics
Genomes and GenesSpecies | David H SmallSummaryAffiliation: University of Tasmania Country: Australia Publications
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Publications
Neural network dysfunction in Alzheimer's disease: a drug development perspectiveDavid H Small
Menzies Research Institute, University of Tasmania, Australia
Drug News Perspect 20:557-63. 2007..This review examines mechanisms of synaptic scaling in the brain and explores prospects for future drug development based on a neural network perspective...- Network dysfunction in Alzheimer's disease: does synaptic scaling drive disease progression?David H Small
Menzies Research Institute, University of Tasmania, Hobart 7000, Tasmania, Australia
Trends Mol Med 14:103-8. 2008..It is suggested that further studies on synaptic scaling in AD could reveal new targets for therapeutic drug development... - Regulation of proBACE1 by glycosaminoglycansDavid H Small
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic, Australia
Neurodegener Dis 5:206-8. 2008..We speculate that proBACE1 can be regulated by endogenous heparan sulfate proteoglycans and that drugs which target this interaction may have value in the treatment of Alzheimer's disease... - The role of Abeta-induced calcium dysregulation in the pathogenesis of Alzheimer's diseaseDavid H Small
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
J Alzheimers Dis 16:225-33. 2009..It is likely that elucidation of the mechanism by which Abeta and presenilin cause Ca(2+) dysregulation in neurons will help to identify new drug targets for the treatment of AD... - Dysregulation of calcium homeostasis in Alzheimer's diseaseDavid H Small
Menzies Research Institute, University of Tasmania, Private Bag 24, Hobart, TAS 7001, Australia
Neurochem Res 34:1824-9. 2009.... - Presenilins and the gamma-secretase: still a complex problemDavid H Small
Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7001, Australia
Mol Brain 3:7. 2010..Unanswered questions about their biochemical mechanism of action and their effects on Ca2+ homeostasis are examined... - Transthyretin oligomers induce calcium influx via voltage-gated calcium channelsXu Hou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
J Neurochem 100:446-57. 2007..These results suggest that increasing [Ca(2+)](i) via VGCCs may be an important early event which contributes to TTR-induced cytotoxicity, and that TTR oligomers, rather than mature fibrils, may be the major cytotoxic form of TTR... - Glycosaminoglycan-induced activation of the beta-secretase (BACE1) of Alzheimer's diseaseDavid W Klaver
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
J Neurochem 112:1552-61. 2010..The results suggest a model in which conformational changes close to the prodomain may be involved in the mechanism of heparin-induced activation of proBACE1... - Inhibition of Abeta aggregation and neurotoxicity by the 39-kDa receptor-associated proteinMegan L Kerr
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia
J Neurochem 112:1199-209. 2010..RAP also blocked an Abeta-induced inhibition of long-term memory consolidation in 1-day-old chicks. This study demonstrates that RAP binds to Abeta and is an inhibitor of the neurotoxic effects of Abeta... - The beta-amyloid protein of Alzheimer's disease binds to membrane lipids but does not bind to the alpha7 nicotinic acetylcholine receptorDavid H Small
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia
J Neurochem 101:1527-38. 2007..Instead, we speculate that Abeta may exert its effects by altering the packing of lipids within the plasma membrane, which could, in turn, influence the function of a variety of receptors and channels on the cell surface... - Effect of heparin on APP metabolism and Abeta production in cortical neuronsDavid Klaver
Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia
Neurodegener Dis 7:187-9. 2010..Several studies suggest that heparin or heparan sulfate analogues may have value as therapeutic agents for the treatment of AD... - Is BACE1 a suitable therapeutic target for the treatment of Alzheimer's disease? Current strategies and future directionsDavid W Klaver
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
Biol Chem 391:849-59. 2010..This review focuses on the structure BACE1, current therapeutic strategies based on developing active-site inhibitors, and new approaches to therapy involving targeting the expression or post-translational regulation of BACE1... - Cholesterol and anionic phospholipids increase the binding of amyloidogenic transthyretin to lipid membranesXu Hou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Biochim Biophys Acta 1778:198-205. 2008..These results suggest that cholesterol and anionic phospholipids may be important for TTR aggregation and TTR-induced cytotoxicity... - Surface plasmon resonance spectroscopy: a new lead in studying the membrane binding of amyloidogenic transthyretinXu Hou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic, Australia
Methods Mol Biol 752:215-28. 2011..In this chapter, we describe the application of SPR to the study of amyloidogenic transthyretin binding to the plasma membrane and artificial lipid bilayers... - Astrocytes in Alzheimer's disease: emerging roles in calcium dysregulation and synaptic plasticityAdele J Vincent
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
J Alzheimers Dis 22:699-714. 2010..Therefore, astrocyte dysfunction may contribute to the earliest neuronal deficits in AD. Here we discuss emerging concepts in glial biology and the implications of astrocyte dysfunction on neurodegeneration in AD... - Memory loss caused by beta-amyloid protein is rescued by a beta(3)-adrenoceptor agonistMarie E Gibbs
Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Wellington Road, Clayton, Victoria 3800, Australia
Neurobiol Aging 31:614-24. 2010..A beta(3)-AR agonist (CL316243), but not a beta(2)-AR agonist, rescued Abeta-induced memory loss, suggesting the need for further studies on the role of beta(3)-ARs in AD... - Effects of heparin and enoxaparin on APP processing and A? production in primary cortical neurons from Tg2576 miceHao Cui
Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
PLoS ONE 6:e23007. 2011..Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower A? plaque deposition and improve cognitive function in AD transgenic mice... - High resolution scanning tunnelling microscopy of the beta-amyloid protein (Abeta1-40) of Alzheimer's disease suggests a novel mechanism of oligomer assemblyDusan Losic
Department of Biochemistry and Molecular Biology, Monash University, Vic. 3800, Australia
J Struct Biol 155:104-10. 2006..The results suggest that the oligomer formation can proceed through a mechanism involving the linear association of monomers... - Surface plasmon resonance spectroscopy in determination of the interactions between amyloid beta proteins (Abeta) and lipid membranesXu Hou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
Methods Mol Biol 627:225-35. 2010..In this chapter, we describe the application of SPR spectroscopy to the determination of the binding of Abeta to lipid membranes... - The beta-amyloid protein of Alzheimer's disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanismSteven Petratos
Molecular Neurobiology Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia
Brain 131:90-108. 2008.... - Transthyretin and familial amyloidotic polyneuropathy. Recent progress in understanding the molecular mechanism of neurodegenerationXu Hou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
FEBS J 274:1637-50. 2007.... - Beta-amyloid fibril formation is promoted by step edges of highly oriented pyrolytic graphiteDusan Losic
Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
Biopolymers 84:519-26. 2006..The results demonstrate that surface interactions can promote the aggregation of Abeta into amyloid fibrils and they suggest that similar interactions could promote amyloid aggregation in vivo... - Surface plasmon resonance for the analysis of beta-amyloid interactions and fibril formation in Alzheimer's disease researchMarie Isabel Aguilar
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia
Neurotox Res 7:17-27. 2005..This article reviews the application of SPR to the study of the molecular interactions associated with AD and how this information enhances our molecular understanding of ABeta -mediated toxicity... - Activation of cathepsin D by glycosaminoglycansMarie Beckman
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
FEBS J 276:7343-52. 2009..However, it is possible that heparin may also activate the proenzyme directly. On the basis of this study, we propose that GAGs may regulate CD activity in vivo... - Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: function, regulation of proteolysis, and implications for drug developmentMegan L Kerr
Laboratory of Molecular Neurobiology, Department of Biochemistry and Molecular Biology, and Monash University Centre for Brain and Behaviour, Monash University, Victoria, Australia
J Neurosci Res 80:151-9. 2005..In this Mini-Review, the role of the cytoplasmic domain of APP in APP trafficking and proteolysis is described. These studies suggest that proteins that bind to the cytoplasmic domain may be important targets for drug development in AD... - Heparin activates beta-secretase (BACE1) of Alzheimer's disease and increases autocatalysis of the enzymeMarie Beckman
Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
Biochemistry 45:6703-14. 2006..Our study provides evidence that heparan sulfate proteoglycans could regulate the rate of Alphabeta production in vivo... - TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neuronsRobert J Gasperini
Menzies Research Institute, University of Tasmania, Tasmania, 7001, Australia
Mol Neurodegener 6:19. 2011..abstract:.. - Mechanisms of synaptic homeostasis in Alzheimer's diseaseDavid H Small
Dept of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
Curr Alzheimer Res 1:27-32. 2004..In this review, several possible mechanisms of synaptic scaling are described... - Acetylcholinesterase inhibitors for the treatment of dementia in Alzheimer's disease: do we need new inhibitors?David H Small
Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Wellington Road, Clayton VIC 3800, Australia
Expert Opin Emerg Drugs 10:817-25. 2005..These new treatments could make AChEI therapy less relevant for treatment of Alzheimer's disease... - Binding of amyloidogenic transthyretin to the plasma membrane alters membrane fluidity and induces neurotoxicityXu Hou
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Biochemistry 44:11618-27. 2005..These results demonstrate that TTR can bind to the plasma membrane and cause a change in membrane fluidity. Altered membrane fluidity may be the cause of the neurotoxicity... - Alois Alzheimer and Alzheimer's disease: a centennial perspectiveDavid H Small
Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
J Neurochem 99:708-10. 2006..In this article, we review the current status of the amyloid hypothesis of AD and its role in the development of future therapy... - Characterization of early stage intermediates in the nucleation phase of a? aggregationJiali Zhai
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
Biochemistry 51:1070-8. 2012..These results are the first reported measurements of the real-time changes in A? molecular structure during the early stages of amyloid formation at the nanometer level... - Alzheimer's disease therapeutics: new approaches to an ageing problemDavid H Small
Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
IUBMB Life 56:203-8. 2004..This review examines the potential of immunization strategies, cholesterol-lowering drugs, protease inhibitors and nicotinic drugs for the treatment of AD... - Do acetylcholinesterase inhibitors boost synaptic scaling in Alzheimer's disease?David H Small
Laboratory of Molecular Neurobiology, Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
Trends Neurosci 27:245-9. 2004..It is suggested that increased cholinergic activity during the early stages of AD contributes to synaptic scaling and that acetylcholinesterase inhibitors improve cognition in AD patients by boosting this mechanism... - Cholinergic regulation of synaptic plasticity as a therapeutic target in Alzheimer's diseaseDavid H Small
Laboratory of Molecular Neurobiology, University of Melbourne, Victoria 3010, Australia
J Alzheimers Dis 4:349-55. 2002..Nicotinic agonists may also protect cells from Abeta toxicity. Drugs which interact with the nAChR or which inhibit Abeta binding to nAChRs may be of value for the treatment of AD... - Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque depositionLisa R Fodero
Laboratory of Molecular Neurobiology, Department of Pathology, The University of Melbourne, Melbourne, Australia
J Neurochem 81:441-8. 2002..The study supports the possibility that glycosylation may also be a useful biomarker of AD... - Acetylcholinesterase is increased in mouse neuronal and astrocyte cultures after treatment with beta-amyloid peptidesJavier Saez-Valero
Instituto de Neurociencias, Universidad Miguel Hernandez CSIC, 03550, San Juan de Alicante, Spain
Brain Res 965:283-6. 2003.... - Changes in molecular isoform distribution of acetylcholinesterase in rat cortex and cerebrospinal fluid after intracerebroventricular administration of amyloid beta-peptideJavier Saez-Valero
Instituto de Neurociencias, Universidad Miguel Hernandez CSIC, 03550 San Juan de Alicante, Spain
Neurosci Lett 325:199-202. 2002..The results support the view that changes in AChE isoform pattern in the AD brain are a direct consequence of A beta accumulation... - Alzheimer's disease biomarkers: their value in diagnosis and clinical trialsDavid H Small
Laboratory of Molecular Neurobiology, Department of Pathology, University of Melbourne, Victoria 3010, Australia
Front Biosci 7:d986-8. 2002..Nevertheless, it may eventually be possible to use several markers in combination to obtain sufficient diagnostic accuracy. However, for this to be the case, new specific biomarkers may need to be identified... - Toxicity of substrate-bound amyloid peptides on vascular smooth muscle cells is enhanced by homocysteineSu San Mok
Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
Eur J Biochem 269:3014-22. 2002..Our studies also suggest that homocysteine, a known risk factor for other cardiovascular diseases, could also be a risk factor for hemorrhagic stroke associated with CAA... - Is gamma-secretase a multienzyme complex for membrane protein degradation? Models and speculationsDavid H Small
Laboratory of Molecular Neurobiology, Department of Pathology, University of Melbourne, Victoria 3010, Australia
Peptides 23:1317-21. 2002..This article presents some models of gamma-secretase and suggests that the simplest interpretation of current data is that gamma-secretase is a complex of several proteases located in the lumen of secretory vesicles... - Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's diseaseJanelle Nunan
Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia
Essays Biochem 38:37-49. 2002..In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease... - Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranesSupundi Subasinghe
Department of Pathology, University of Melbourne, Victoria, Australia
J Neurochem 84:471-9. 2003..Reduction of membrane cholesterol using cholesterol-lowering drugs may be of therapeutic benefit because it reduces Abeta-membrane binding... - Beta-amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pHGenevieve M J A Klug
Department of Pathology, University of Melbourne, Victoria, Australia
Eur J Biochem 270:4282-93. 2003..4 was more cytotoxic than Abeta aged at pH 5.0. Taken together, the results suggest that Abeta oligomerizes via two mutually exclusive mechanisms to form two different types of aggregates, which differ in their cytotoxic properties... - Proteasome-mediated degradation of the C-terminus of the Alzheimer's disease beta-amyloid protein precursor: effect of C-terminal truncation on production of beta-amyloid proteinJanelle Nunan
Department of Pathology, University of Melbourne, Victoria, Australia
J Neurosci Res 74:378-85. 2003..Therefore, the proteasome-dependent trafficking pathway of APP may be a valid therapeutic target for altering Abeta production in the Alzheimer's disease brain...