Capturing intracellular Ca2+ dynamics in computational models of neurodegenerative diseases

Abstract

Many signaling pathways crucial for homeostatic regulation, synaptic plasticity, apoptosis and immune response depend on Ca²⁺. Ca²⁺ dysregulation disrupts normal function of neurons and neuronal networks. This causes severe motor and cognitive disabilities. Understanding how Ca²⁺ dysregulation triggers disease onset and progression, and affects downstream processes, can help identify targets for treatments. Because of intermingling of molecular pathways, dissecting the role of individual mechanisms and establishing causality is very challenging. Computational models provide a way to decipher these processes. I review some computational models with Ca²⁺ dynamics to illustrate their predictive power, and note where extending those models to capture multiscale interaction of Ca²⁺ dependent molecular pathways can be useful for therapeutic and drug discovery purposes.