Category: Diseases, Type: Understanding
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We are particularly interested in the biochemical events that occur in the early stages of Alzheimer’s disease. As such we have identified two mitochondrial proteins (ABAD and CypD) that bind the toxic beta-amyloid peptide resulting in some of the toxic events that occur in Alzheimer’s disease. We have shown that if this binding of beta-amyloid peptide to ABAD or CypD can be prevented, then this can improve and reverse some of the events that occur in Alzheimer’s disease. As part of these studies we have identified genes which become activated due to this binding of beta-amyloid peptide to ABAD, and shown that they are also activated in humans.
Our current approaches are:1) analyse the chemical signalling pathways that are activated in Alzheimer’s disease2) identify small molecule compounds that bind to ABAd and CypD and develop these into potential drug therapies
We are therefore very interested in the following technical issues:
Schemes and typical results
Special features and limitations
Muirhead K, Borger E, Aitken L, Conway S & Gunn-Moore FJ (2010) The consequences of intracellular beta-amyloid in Alzheimer’s disease. Biochemical Journal In press
Du H, Guo L, Fang F, Chen D, Sosunov A, McKhann G, Yan Y, Wang C, Zhang H, Molkentin J, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen J & Yan SD Deficiency of Cyclophilin D attenuates mitochondrial and neuronal perturbation, and ameliorates learning memory in Alzheimer’s disease (2008) Nature Medicine. 14(10) 1097-105
Ren Y, Fang F, Davey F, Taylor M, Aiton J, Coote P, Yao J, Chen JX, Yan SD & Gunn-Moore FJ. Endophilin I expression is increased in the brains of Alzheimer’s disease patients. (2008) Journal of Biological Chemistry, 283, 5685-91.
Gunn-Moore D, McVee J, Bradshaw J, Pearson G, Head E & Gunn-Moore F b-Amyloid and hyperphosphorylated tau deposition in cat brains. (2006) Journal of Feline Medicine & Surgery, 8, 234-42
Lustbader J., Cirilli M., Lin, C., Xu HW., Takuma K., Wang N., Caspersen C., Chen X., Pollack S., Chaney M., Trinchese F., Liu S., Gunn-Moore F., Lue L-F., Walker D., Kuppusamy P., Zewier Z., Arancio O., Stern D., Yan SD. & Wu H. (2004) ABAD directly links Ab to mitochondrial toxicity in Alzheimer's disease. Science, 304, 448-52.
Powell A.J., Read J.A., Banfield M.J., Gunn-Moore F., Yan S.D., Lustbader J., Stern A.R., Stern D.M. & Brady R.L. (2000) Recognition of structurally diverse substrates by type II 3-hydroxyacyl-CoA dehydrogenase (HADH II)/amyloid-beta binding alcohol dehydrogenase (ABAD). Journal of Molecular Biology, 303(2), 311-27.
What biological process are you investigating?
What equipment do you use?
Microscopes, lasers, SPR, ITC, thermal shift, crystallography
What analytes do you measure?
Biochemical signaling and inhibitors
What chemicals (fluorophores, labels, ...) do you use to measure your analytes / signatures? Or is it label free? Examples: fluorescence, Raman, SHG
|2||Stevenson David||2010-01-28 20:25||View|
|1||Stevenson David||2010-01-28 20:24|
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