Alzheimer’s Disease

Name

Description

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:
1) How to get test compounds into mammalian cells2) Novel methods for analysing protein-protein interactions3) measuring in vivo mitochondrial function4) producing protein crystals for establishing molecular structures5) the molecular structures of beta-amyloid

Schemes and typical results

Special features and limitations

Publications

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.

1. Yao Y, Taylor M, Davey F, RenY, Aiton J , Coote P, Chen X, Yan SD & Gunn-Moore FJ. Interaction of Amyloid binding Alcohol Dehydrogenase/Aβ mediates up-regulation of peroxiredoxin II in the brains of Alzheimer’s disease patients and a transgenic Alzheimer’s disease mouse model. (2007) Molecular and Cellular Neuroscience, 35, 377–82

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?

Alzheimer’s disease

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

Fluorescence

Expert(s)

Fixed keywords

Free keywords

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