Effect of disturbances in neuronal calcium and IP3 dynamics on β-amyloid production and degradation.

Abstract

Overproduction and accumulation of β-amyloid and its improper clearance can cause neurotoxicity leading to Alzheimer's disease. The production and degradation of β-amyloid depend on the calcium ([Ca2+]) and IP3 dynamics in the nerve cells. Thus, there is a need to understand the impacts of disturbances in the processes of [Ca2+] and IP3 dynamics on β-amyloid production and its degradation. Here, a model is proposed to investigate the role of [Ca2+] and IP3 dynamics on β-amyloid production and degradation. The problem is formulated in terms of the initial boundary value problem involving the system of two reaction-diffusion equations respectively for [Ca2+] and IP3 in the nerve cell. The solution is obtained by employing the Finite element approach. The numerical results are used to analyze the impact of various mechanisms of calcium and IP3 dynamics on β-amyloid production and degradation in a neuron cell. The results indicate that disturbances in any of the constitutive processes of interdependent calcium and IP3 dynamics like source influx, buffering, serca pump, and IP3 dynamics, etc. can cause dynamic changes in β-amyloid production and degradation, which in turn can be the cause of neurotoxicity and neuronal disorders like Alzheimer's disease. Thus, the relationships obtained by the proposed model among various mechanisms can be useful in addressing the challenges of identifying specific constitutive processes causing neuronal disorders like Alzheimer's disease, etc., and developing the framework for their diagnosis and treatment.