Professor Colin Masters
Position: Executive Director, Mental Health Research Institute and
Laureate Professor, University of Melbourne
Alzheimer's disease: Structure, function and processing of the amyloid precursor protein of Alzheimer's disease. Identifying genetic and environmental factors relevant to the metabolism of the amyloid precursor protein and the biogenesis of amyloid. Therapeutic strategies for Alzheimer's disease based on this knowledge.
Prion diseases: including Creutzfeldt-Jakob disease, Parkinson's disease, Huntington's disease
Current studies on Alzheimer's disease are now focused on identifying the pathways through which environmental and genetic factors can operate to cause this disease. In collaboration with the pharmaceutical industry and biotechnology enterprises, a multidisciplinary approach is now directed at identifying lead compounds which can inhibit the production or aggregation of amyloid in the Alzheimer's disease brain: a new class of protease inhibitors has been identified which has very promising activity in vitro and will be evaluated in human trials. Commercial development of compounds which are directed at the toxicity of the A-beta amyloid has commenced. A phase II clinical trial of a metal chelating compound aimed at mobilizing the amyloid A-beta from the Alzheimer's disease brain has also been completed following the demonstration of efficacy of this compound in a transgenic mouse model of Alzheimer's disease.
Knowledge gained from the Alzheimer's disease arena is being transferred to Creutzfeldt-Jakob disease/prion diseases, Parkinson's disease, and other related degenerations.
(Top 10 cited publications, updated June 2010)
Kang J, Lemaire H-G, Unterbeck A, Salbaum MJ, Masters CL, Grzeschik K-H, Multhaup G, Beyreuther K, Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell surface receptor. Nature 1987; 325:733-736. (3121 citations)
Masters CL, Simms G, Weinman NA, McDonald BL, Multhaup G, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Nat Acad Sci USA 1985; 82:4245-4249. (2203 citations)
Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell 1989; 57:115-126. (980 citations)
Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 1985; 4:2757-2763. (695 citations)
Bush AI, Pettingell WH, Multhaup G, D. Paradis M, Vonsattel J-P, Gusella JF, Beyreuther K, Masters CL, Tanzi RE. Rapid induction of Alzheimer A amyloid formation by zinc. Science 1994; 265:1464-1467. (608 citations)
McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL. Soluble pool of Aβ as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 1999; 46:860-866. (580 citations)
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, Tanzi RE, Masters CL, Bush AI. Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 2001, 30:665-676 [and see Previews: Gouras GK, Beal MF. Metal chelator decreases Alzheimer β-amyloid plaques. Neuron 2001; 30:641-642]. (498 citations)
Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K, Fischer P, Masters CL, Price DL. Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci USA 1990; 87:1561-1565. (498 citations)
Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuther K. Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer’s disease. J Mol Biol 1991; 218:149-163. (466 citations)
Masters CL, Harris JO, Gajdusek DC, Gibbs CJ Jr, Bernoulli C, Asher DM. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1979; 5:177-188. (447 citations)