Journal Article

Effects of Specific Inhibitors for CaMK1D on a Primary Neuron Model for Alzheimer’s Disease

Kumar, Jitendra, Kar, Satyabrata, Overduin, Michael, Grant, Paige

2021

Overview

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Despite extensive research and targeting of the main molecular components of the disease, beta-amyloid (Aβ) and tau, there are currently no treatments that alter the progression of the disease. Here, we examine the effects of two specific kinase inhibitors for calcium/calmodulin-dependent protein kinase type 1D (CaMK1D) on Aβ-mediated toxicity, using mouse primary cortical neurons. Tau hyperphosphorylation and cell death were used as AD indicators. These specific inhibitors were found to prevent Aβ induced tau hyperphosphorylation in culture, but were not able to protect cells from Aβ induced toxicity. While inhibitors were able to alter AD pathology in cell culture, they were insufficient to prevent cell death. With further research and development, these inhibitors could contribute to a multi-drug strategy to combat AD.

• Publisher: MDPI AG,MDPI
• Subject: Alzheimer Disease - drug therapy / Alzheimer Disease - metabolism / Alzheimer Disease - pathology / Alzheimer's disease / Amyloid beta-Peptides - antagonists & inhibitors / Amyloid beta-Peptides - metabolism / Animals / beta-amyloid / Calcium-Calmodulin-Dependent Protein Kinase Type 1 - antagonists & inhibitors / Calcium-Calmodulin-Dependent Protein Kinase Type 1 - metabolism / CaMK1D / Cell culture / Cell Survival - drug effects / Cells, Cultured / Clinical trials / Cytotoxicity / Disease Models, Animal / Gene expression / Homeostasis / Hypotheses / kinase inhibitor / Kinases / Mice / Mice, Inbred BALB C / Models, Molecular / Neurons / Neurons - drug effects / Neurons - metabolism / Neurons - pathology / Peptides / Phosphorylation / Protein Kinase Inhibitors - chemistry / Protein Kinase Inhibitors - pharmacology / Proteins / tau phosphorylation / Toxicity