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| First Name: | Ashley | | Last Name: | Bush | | Title: | Associate Professor of Psychiatry | | Advanced Degrees: | MD, PhD | | Affiliation: | Massachusetts General Hospital | | Department: | Psychiatry | | Street Address 1: | Laboratory for Oxidation Biology | | Street Address 2: | Bldg 114, 16th Street | | City: | Charlestown | | State/Province: | MA | | Zip/Postal Code: | 02129 | Country/Territory: | U.S.A. | | Phone: | 617-726-8244 | | Fax: | 617-724-1823 | | Email Address: |  |
Disclosure:
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View all comments by Ashley Bush
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Aging Process, Polyglutamine Disorders (Huntington's, etc.), Prion Diseases, Stroke and Trauma, Tauopathies, Alzheimer Disease, Neurodevelopmental Disorders (Down syndrome, etc.), Neuromuscular Disorders (ALS, etc.), Parkinson Disease
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Drug screening, Proteomics, A-beta PP/A-beta, Molecular and Cell biology, Brain imaging, Chemistry/Pharmacology, Clinical trials, Protein structure/chemistry, Animal Models, Neurobiology, Neuropathology, Neurotransmission, Oxidative Stress, Metals
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Ashley I. Bush (MD, 1982; PhD, 1992; University of Melbourne, Australia) is the Director of the Laboratory for Oxidation Biology, Massachusetts General Hospital; Associate Professor of Psychiatry at Harvard Medical School; and Principal Research Fellow at the Mental Health Research Institute of Victoria, Australia. A board certified psychiatrist, he trained in psychoanalysis, then took out a PhD in neuroscience with Colin Masters at the University of Melbourne, and did a post-doc with Rudy Tanzi at Harvard. He is the recipient of several awards including the Harkness Fellowship from the Commonwealth Fund of New York, the Beeson Award from the Alliance for Aging Research and the Senator John Hatfiield Award for Clinical Research from the Alzheimer Association, and has authored over 100 publications. His laboratory uncovered the interaction of biometals (copper, zinc and iron) with beta-amyloid that contributes to both oxidation damage and amyloid accumulation in Alzheimer's disease. This has lead to the development of novel therapeutic compounds that are currently in clinical trials. The laboratory has generalized its findings into the corruption of metalloproteins contributing to the pathogenesis of other age-dependent neurodegenerative disorders, Parkinson's disease, ALS, TSE and cataracts. |
1. Bush AI, Martins RN, Rumble B, Moir R, Fuller S, Milward E, Currie J, Ames D, Weidemann A, Fischer P, Multhaup G, Beyreuther K, Masters CL. The amyloid precursor protein of Alzheimer's Disease is released by human platelets. Journal of Biological Chemistry 1990; 265, 15977-15983.
2. Bush AI, Pettingell W, Paradis MdP, Tanzi RE. Modulation of Aß adhesiveness and secretase site cleavage by zinc. Journal of Biological Chemistry. 1994; 269, 12152-12158.
3. Bush AI, Pettingell WH, Multhaup G, Paradis Md, Vonsattel J-P, Gusella JF, Beyreuther K, Masters CL, Tanzi RE. Rapid induction of Alzheimer Ab amyloid formation by zinc. Science. 1994; 265, 1464-1467.
4. Atwood CS, Moir RD, Huang X, Bacarra NME, Scarpa RC, Romano DM, Hartshorn MA, Tanzi RE, Bush AI. Dramatic aggregation of Alzheimer Aß by Cu(II) is induced by conditions representing physiological acidosis. Journal of Biological Chemistry 1998; 273, 12817-12826.
5. Cherny RA, Legg JT, McLean CA, Fairlie DP, Huang X, Atwood CS, Tanzi RE, Masters CL, Bush AI. Aqueous dissolution of Alzheimer's disease Aß amyloid deposits by biometal depletion. Journal of Biological Chemistry 1999, 274, 23223-23228.
6. Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall J, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI. Cu(II) potentiation of Alzheimer Aß neurotoxicity: correlation with cell-free hydrogen peroxide production and metal reduction. Journal of Biological Chemistry 1999, 274, 37111-37116.
7. Atwood CS, Scarpa RC, Huang X, Moir RD, Jones WD, Fairlie DP, Tanzi RE, Bush AI, Characterization of Copper Interactions with Alzheimer Aß Peptides- Identification of an Attomolar Affinity Copper Binding Site on Aß1-42. Journal of Neurochemistry 2000;75 1219-1233.
8. Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Masters CL, Bush AI, Barnham KJ Alzheimer's disease amyloid- binds Cu and Zn to generate an allosterically-ordered membrane-penetrating structure containing SOD-like subunits. Journal of Biological Chemistry 2001; 276, 20466-20473.
9. Cherny RA, Atwood CS, Xilinas X, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y-S, Huang X, Goldstein LE, Moir RD, Lim JT, Zheng H, Beyreuther K, Tanzi RE, Masters CL, Bush AI. Treatment with a copper-zinc chelator markedly and rapidly inhibits ß-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron, 2001; 30, 665-676.
10. Opazo C, Huang X, Cherny RA, Moir RD, Roher AE, White AR, Cappai R, Masters CL, Tanzi RE, Inestrosa NC, Bush AI. Metalloenzyme-like activity of Alzheimer's disease ß-amyloid: Cu-dependent catalytic conversion of dopamine, cholesterol and biological reducing agents to neurotoxic H2O2. Journal of Biological Chemistry. 2002; 77, 40302-40308. |
The neurochemistry of aging that makes it a risk factor. |
Morgan, D. M., Dong, J., Jacob, J., Lu, K., Apkarian, R. P., Thiyagarajan, P., and Lynn, D. G. (2002). Metal switch for amyloid formation: insight into the structure of the nucleus. J Am Chem Soc 124.
Lee, J.-Y., Cole, T. B., Palmiter, R. D., Suh, S. W., and Koh, J.-Y. (2002). Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci U S A 99, 7705-7710.
Valente, T., and Auladell, C. (2002). Developmental expression of ZnT3 in mouse brain: correlation between the vesicular zinc transporter protein and chelatable vesicular zinc (CVZ) cells. Glial and neuronal CVZ cells interact. Mol Cell Neurosci 21, 189-204. |
I am already quite happily occupied. Perhaps I would consult on increasing the speed, and improving the economy, of international passenger aircraft. |
Amyloid deposition, and associated oxidative damage, is caused by a fatigue in intrinsic brain metal (copper, zinc, iron) homeostasis and consequent reaction of these metals with beta-amyloid. |
Shouldn't we be working by trying to disprove hypothesis? |
Something Shakespeare said in Macbeth. |
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