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Evidence for a selective decrease in type 1 phosphatidylinositol kinase activity in brains of patients with
J Bothmer1, M Markerink, J Jolles
1Department of Neuropsychology and Psychobiology, University of Limburg, Maastricht, The Netherlands.
Dementia (Basel, Switzerland)
|January 1, 1994
Summary
Alzheimer's disease (AD) brains show significantly reduced phosphatidylinositol (PI) kinase activity, specifically PI 3-kinase. This enzyme is crucial for cytoskeletal regulation, suggesting a new therapeutic target for AD.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Phosphatidylinositol (PI) kinase activity is reduced in Alzheimer's disease (AD) brain cytosols.
- Phosphatidylinositol phosphate (PIP) kinase activity remains unaffected in AD.
Purpose of the Study:
- To identify the specific PI kinase affected in AD.
- To characterize the properties of the affected PI kinase.
Main Methods:
- Enzyme activity assays on cytosolic fractions from AD and control brains.
- Differential solubilization and characterization of PI kinase activity.
- Assessment of inhibition by Triton X-100 and adenosine.
Main Results:
- PI kinase activity was significantly decreased (70%) in salt-solubilized fractions from AD temporal cortex.
- PI kinase in salt-solubilized fractions showed high sensitivity to Triton X-100 inhibition and adenosine insensitivity.
- These characteristics identify the affected enzyme as PI 3-kinase (type 1 PI kinase).
Conclusions:
- The study identifies PI 3-kinase as the specific PI kinase affected in Alzheimer's disease.
- Reduced PI 3-kinase activity in AD may impact cytoskeletal regulation.
- Targeting PI 3-kinase could offer a novel therapeutic strategy for AD.