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阿尔茨海默病进程中缺血时神经元钙和 IP 信号系统调节 ATP 释放的机制研究。

Mechanistic insights of neuronal calcium and IP signaling system regulating ATP release during ischemia in progression of Alzheimer's disease.

机构信息

Department of Mathematics, Bioinformatics and Computer Applications, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh, 462003, India.

出版信息

Eur Biophys J. 2023 Apr;52(3):153-173. doi: 10.1007/s00249-023-01660-1. Epub 2023 May 24.

Abstract

The mechanisms of calcium ([Ca]) signaling in various human cells have been widely analyzed by scientists due to its crucial role in human organs like the heartbeat, muscle contractions, bone activity, brain functionality, etc. No study is reported for interdependent [Ca] and IP mechanics regulating the release of ATP in neuron cells during Ischemia in Alzheimer's disease advancement. In the present investigation, a finite element method (FEM) is framed to explore the interdependence of spatiotemporal [Ca] and IP signaling mechanics and its role in ATP release during Ischemia as well as in the advancement of Alzheimer's disorder in neuron cells. The results provide us insights of the mutual spatiotemporal impacts of [Ca] and IP mechanics as well as their contributions to ATP release during Ischemia in neuron cells. The results obtained for the mechanics of interdependent systems differ significantly from the results of simple independent system mechanics and provide new information about the processes of the two systems. From this study, it is concluded that neuronal disorders cannot only be simply attributed to the disturbance caused directly in the processes of calcium signaling mechanics, but also to the disturbances caused in IP regulation mechanisms impacting the calcium regulation in the neuron cell and ATP release.

摘要

由于钙 ([Ca]) 信号在人类心脏、肌肉收缩、骨骼活动、大脑功能等器官中的关键作用,科学家们广泛分析了各种人类细胞中的钙信号机制。目前尚未有研究报道钙依赖性 [Ca] 和 IP 力学在阿尔茨海默病进展过程中的神经元细胞缺血时调节 ATP 释放的情况。在本研究中,构建了一个有限元方法 (FEM) 来探索钙和 IP 信号力学的时空依赖性及其在缺血时以及在神经元细胞中阿尔茨海默病进展过程中 ATP 释放的作用。结果为我们提供了相互作用的时空影响的见解 [Ca] 和 IP 力学以及它们在缺血期间神经元细胞中 ATP 释放的贡献。相互依赖系统力学的结果与简单独立系统力学的结果有很大的不同,并提供了有关这两个系统过程的新信息。从这项研究中可以得出结论,神经元紊乱不仅可以归因于钙信号力学过程中直接引起的干扰,也可以归因于干扰 IP 调节机制,从而影响神经元细胞中的钙调节和 ATP 释放。

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