- 20 views
- 18 downloads
The Role of CaMK1D in Alzheimer's Disease
-
- Author / Creator
- Grant, Paige
-
Alzheimer’s Disease (AD) is an insidious, progressive neurodegenerative disease responsible for the majority of dementia cases worldwide. Despite extensive research and clinical trials, there are currently no approved treatments that alter the progression of the disease. Treating classic molecular targets of AD, amyloid-beta (Aβ) and tau, have not been successful in clinical trials. Further exploration of the disease pathways and of new targets are needed to find effective disease-altering treatments for AD. Here, the role of calcium/calmodulin-dependent protein kinase type 1D (CaMK1D) in AD is examined. While CaMK1D has been implicated in AD in numerous genetic studies, little research has been done at the protein level. In this thesis, mouse primary neuron cultures treated with Aβ oligomers are used as a model system for AD, and specific inhibitors for CaMK1D are used to suppress CaMK1D activity in these cultures. These specific inhibitors are characterized kinetically by surface plasmon resonance, and found to have nanomolar level dissociation constants. Western blotting is used to examine Aβ-induced changes in CaMK1D, tau, and Cyclic AMP responsive element binding protein 1 (CREB), a CaMK1D substrate, and cell viability assays are used to examine cell death in culture. The cleavage and phosphorylation state of CaMK1D was unchanged. CaMK1D specific inhibitors were found to ablate Aβ-induced changes to CREB and tau phosphorylation, but did not protect the cells from Aβ-induced toxicity. Aberrant CaMK1D activity is shown to be a potential contributor to AD, but inhibition of this activity is insufficient to protect neurons from death.
-
- Subjects / Keywords
-
- Graduation date
- Spring 2022
-
- Type of Item
- Thesis
-
- Degree
- Master of Science
-
- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.