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| First Name: | David | | Last Name: | Allsop | | Title: | Professor | | Advanced Degrees: | B.Sc. hons, Ph.D. | | Affiliation: | Lancaster University, UK | | Department: | Biological Sciences | | Street Address 1: | Bailrigg Campus | | City: | Lancaster | | State/Province: | Lancs. | | Zip/Postal Code: | LA1 4YQ | Country/Territory: | United Kingdom | | Phone: | 44-1524-592122 | | Fax: | 44-1524-843854 |
Disclosure:
(view policy)
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Member reports no financial or other potential conflicts of interest. [Last Modified: 22 November 2004]
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View all comments by David Allsop
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Polyglutamine Disorders (Huntington's, etc.), Prion Diseases, Alzheimer Disease, Parkinson Disease
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A-beta PP/A-beta, Molecular and Cell biology, Neuropathology, Clinical trials, Diagnosis, Drug screening, Microscopy, Neurobiology, Chemistry/Pharmacology, Oxidative Stress, Protein structure/chemistry, Genetics
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CURRENT POSITION:
Professor of Neuroscience, Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ.
EMPLOYMENT HISTORY:
1998-2002, Senior Lecturer in Biomedicine, Department of Biological Sciences, Lancaster University, UK.
1994-1998, Assistant Director, Molecular Neuropathology Research, SmithKline Beecham Pharmaceuticals, UK.
1990-1993, Lecturer in Biochemistry, School of Biology and Biochemistry, The Queen's University of Belfast, Northern Ireland, UK.
1988-1990, Visiting Scientist, Psychiatric Research Institute of Tokyo, Tokyo, Japan.
1986-1988, Recipient of a Fellowship from The John Douglas French Foundation for Alzheimer's Disease to work in the laboratory of Dr. G.G. Glenner, Department of Pathology, The University of California at San Diego, USA.
1980-1986, Postdoctoral Research Fellow, Department of Biochemistry, The University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK.
I have a long-standing interest (25 years) in the role of amyloid proteins in Alzheimer's disease and other neurodegenerative disorders. Includes early research experience with Dr. Michael Kidd (at Nottingham University, UK), where I was the first person to isolate amyloid plaque 'cores' from frozen brain tissue and raise monoclonal antibodies to beta-amyloid, and also with Dr. George Glenner (at UCSD, USA). I also spent five years in the pharmaceuticals industry, with SmithKline Beecham (now GSK). |
Allsop D., Landon M. & Kidd M. (1983) The isolation and amino acid composition of senile plaque core protein. Brain Res. 259, 348-352.
Allsop D., Landon M., Kidd M., Lowe J.S., Reynolds G.P. & Gardner A. (1986) Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease. Neurosci. Lett. 68, 252-256.
Allsop D., Haga S., Haga C., Ikeda S., Mann D.M.A. & Ishii T. (1989) Early senile plaques in Down's syndrome brains show a close relationship with cell bodies of neurons. Neuropathol. Appl. Neurobiol. 15, 531-542.
Robert G.W., Allsop D. & Bruton C. (1990) The occult aftermath of boxing. J. Neurol. Neurosurg. Psych. 53, 373-378.
Hardy J. & Allsop D. (1991) Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol. Sci. 12, 383-388.
Hartmann T., Bieger S.C., Bruhl B., Tienari P.J., Ida N., Allsop D., Roberts G.W., Masters C.L., Dotti C.G., Unsicker K. & Beyreuther K. (1997) Distinct sites of intracellular production for Alzheimer's disease beta40/42 amyloid peptides. Nature (Med.) 3, 1016-1020.
Turnbull S., Tabner B.J., Moore S., Davies Y., El-Agnaf O.M.A. & Allsop D. (2001) alpha-synuclein implicated in Parkinson’s disease catalyses the formation of hydrogen peroxide in vitro. Free Radical Biol. Med. 30, 1163-1170.
Turnbull, S., Tabner, B.J., Brown, D.R. & Allsop, D. (2003) Copper-dependent generation of hydrogen peroxide from the toxic prion protein fragment PrP106-126. Neurosci. Lett. 336, 159-162.
El-Agnaf, O.M.A., Salem, S.S., Paleologou, K.E., Gibson, M.J., Curran, M.D., Court, J.A., Mann, D.M.A., Ikeda, S.I., Cookson, M.R., Hardy, J. & Allsop, D. (2003) α-Synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. FASEB J. 17, 1945-1947.
El-Agnaf O.M.A., Paleologou K.E., Greer B., Abogrein A.M., King J.E., Salem S.A., Fullwood N.J., Benson F.E., Hewitt R., Ford K.J., Martin F.L., Harriott P., Cookson M.R. & Allsop D. (2004) A strategy for designing inhibitors of α-synuclein aggregation and toxicity as a novel treatment for Parkinson's disease and related disorders. FASEB J. 18, 1315-1317.
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What is the major cause of neurodegeneration in the brain in Alzheimer's disease? Is it early-stage beta-amyloid deposition, the formation of neurofibrillary tangles, oxidative stress, inflammation, a combination of these things, or something else? |
Tsai J, Grutzendler J, Duff K, Gan W-B. Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nat Neurosci. 2004 Nov;7(11):1181-3.
Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003 Apr 18;300(5618):486-9.
Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature. 2004 Oct 14;431(7010):805-10.
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A complete study of the role of metals, hydrogen peroxide and free radicals in the aggregation and toxicity of all of the various amyloids found in human disease, including those outside of the brain (a lifetime's work).
Further study of the role of metal binding in the aggregation and toxicity of alpha-synuclein.
Testing of the peptide-based inhibitors of alpha-synuclein aggregation described in our recent paper [El-Agnaf et al. (2004) A strategy for designing inhibitors of alpha-synuclein aggregation and toxicity as a novel treatment for Parkinson's disease and related disorders. FASEB J. 18, 1315-1317] in transgenic mice and then in human clinical trials.
Full study of the possibility of using alpha-synuclein in human plasma [El-Agnaf et al. (2003) alpha-Synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. FASEB J. 17, 1945-1947] as a diagnistic marker for synuclein diseases.
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Our leading hypothesis is that the generation of hydrogen peroxide and, subsequently, hydroxyl radicals, from an aggregating protein is a common mechanism of oxidative stress and resultant cell death in various neurodegenerative diseases, and possibly other forms of amyloidosis as well. This property of at least some amyloids seems to be related to their ability to bind to redox-active transition metal ions. |
So far we have evidence that then above applies to beta-amyloid, alpha-synuclein and the prion protein. We need to look at many other amyloidogenic proteins and peptides as well. Also, the key question is:- Is this just an interesting property of the isolated amyloid protein, or does it really have relevance to cell death in vivo? |
That our hypothesis might just apply to a small selection of amyloid-forming proteins, i.e. those that happen to interact with metals. Also, although we believe that our hypothesis can explain the toxicity of various amyloids in cell model systems, the formation of hydrogen peroxide might not be a major cause of cell death in vivo. It might just be one of a number of multiple causes. |
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