Alterations in the activity of adenylate cyclase and high affinity GTPase in Alzheimer's disease

Ross, B. M., McLaughlin, M. , Roberts, M., Milligan, G. , McCulloch, J. and Knowler, J. T. (1993) Alterations in the activity of adenylate cyclase and high affinity GTPase in Alzheimer's disease. Brain Research, 622(1-2), pp. 35-42. (doi:10.1016/0006-8993(93)90798-R) (PMID:8242380)

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Abstract

The aim of this study was to assess the effect that Alzheimer's disease has on the functional integrity of several signal transduction proteins. The relative levels of the G-protein α subunits Gsα-L, Gsα-S, Giα-1, Giα-2 and Goα were measured by western blotting and found to be unchanged in membranes prepared from Alzheimer-diseased frontal cortex or hippocampus compared to control brains. However the activity of the G-protein associated enzyme, high affinity GTPase, was found to be reduced in the frontal cortex (reduced by 25%) and by a similar magnitude in the hippocampus (reduced by 27%) of Alzheimer subjects. The same membrane preparation were also assayed for the activity of adenylate cyclase. Basal enzyme activity was not significantly altered in Alzheimer diseased hippocampus, but was markedly reduced (by 45%) in the frontal cortex. The ability of fluoride and aluminum ions to stimulate adenylate cyclase was not significantly changed in either brain region. This suggests that G-proteins, especially Gs, are still able to interact with this enzyme. These results indicate that although the presence of Alzheimer's disease does not significantly alter G-protein levels, changes have taken place in the overall activity of these proteins. However this alteration does not affect their ability to stimulate adenylate cyclase activity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McCulloch, Mr James and McLaughlin, Dr Mark and Milligan, Professor Graeme and Roberts, Dr Margaret
Authors: Ross, B. M., McLaughlin, M., Roberts, M., Milligan, G., McCulloch, J., and Knowler, J. T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Brain Research
Publisher:Elsevier
ISSN:0006-8993
ISSN (Online):1872-6240

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