What can computational modeling offer for studying the Ca(2+) dysregulation in Alzheimer's disease: current research and future directions

Ca(2+) dysregulation is an early event observed in Alzheimer’s disease (AD) patients preceding the presence of its clinical symptoms. Dysregulation of neuronal Ca(2+) will cause synaptic loss and neuronal death, eventually leading to memory impairments and cognitive decline. Treatments targeting Ca(2+) signaling pathways are potential therapeutic strategies against AD. The complicated interactions make it challenging and expensive to study the underlying mechanisms as to how Ca(2+) signaling contributes to the pathogenesis of AD. Computational modeling offers new opportunities to study the signaling pathway and test proposed mechanisms. In this mini-review, we present some computational approaches that have been used to study Ca(2+) dysregulation of AD by simulating Ca(2+) signaling at various levels. We also pointed out the future directions that computational modeling can be done in studying the Ca(2+) dysregulation in AD.