Pawar Anand, Pardasani Kamal Raj
Department of Mathematics, Bioinformatics, and Computer Applications, MANIT, Bhopal, Madhya Pradesh 462003 India.
Cogn Neurodyn. 2023 Feb;17(1):239-256. doi: 10.1007/s11571-022-09815-0. Epub 2022 May 17.
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 ([Ca]) and IP3 dynamics in the nerve cells. Thus, there is a need to understand the impacts of disturbances in the processes of [Ca] and IP3 dynamics on β-amyloid production and its degradation. Here, a model is proposed to investigate the role of [Ca] 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 [Ca] 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.
β-淀粉样蛋白的过度产生和积累及其清除不当会导致神经毒性,进而引发阿尔茨海默病。β-淀粉样蛋白的产生和降解取决于神经细胞中的钙([Ca])和肌醇三磷酸(IP3)动态变化。因此,有必要了解[Ca]和IP3动态变化过程中的干扰对β-淀粉样蛋白产生及其降解的影响。在此,提出一个模型来研究[Ca]和IP3动态变化对β-淀粉样蛋白产生和降解的作用。该问题被表述为一个初始边界值问题,涉及分别针对神经细胞中[Ca]和IP3的两个反应扩散方程组。通过采用有限元方法获得解。数值结果用于分析钙和IP3动态变化的各种机制对神经元细胞中β-淀粉样蛋白产生和降解的影响。结果表明,相互依赖的钙和IP3动态变化的任何组成过程中的干扰,如源流入、缓冲、肌浆网钙ATP酶泵和IP3动态变化等,都可能导致β-淀粉样蛋白产生和降解的动态变化,这反过来可能是神经毒性和诸如阿尔茨海默病等神经紊乱的原因。因此,所提出的模型在各种机制之间获得的关系,对于应对识别导致诸如阿尔茨海默病等神经紊乱的特定组成过程的挑战,以及开发其诊断和治疗框架可能是有用的。