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线粒体在帕金森病和其他神经退行性疾病中普遍存在的作用。

The ubiquitous role of mitochondria in Parkinson and other neurodegenerative diseases.

作者信息

Theocharopoulou Georgia

机构信息

Department of Informatics, Ionian University, Plateia Tsirigoti 7, 49100, Corfu, Greece.

出版信息

AIMS Neurosci. 2020 Mar 25;7(1):43-65. doi: 10.3934/Neuroscience.2020004. eCollection 2020.

Abstract

Orderly mitochondrial life cycle, plays a key role in the pathology of neurodegenerative diseases. Mitochondria are ubiquitous in neurons as they respond to an ever-changing demand for energy supply. Mitochondria constantly change in shape and location, feature of their dynamic nature, which facilitates a quality control mechanism. Biological studies in mitochondria dynamics are unveiling the mechanisms of fission and fusion, which essentially arrange morphology and motility of these organelles. Control of mitochondrial network homeostasis is a critical factor for the proper function of neurons. Disease-related genes have been reported to be implicated in mitochondrial dysfunction. Increasing evidence implicate mitochondrial perturbation in neuronal diseases, such as AD, PD, HD, and ALS. The intricacy involved in neurodegenerative diseases and the dynamic nature of mitochondria point to the idea that, despite progress toward detecting the biology underlying mitochondrial disorders, its link to these diseases is difficult to be identified in the laboratory. Considering the need to model signaling pathways, both in spatial and temporal level, there is a challenge to use a multiscale modeling framework, which is essential for understanding the dynamics of a complex biological system. The use of computational models in order to represent both a qualitative and a quantitative structure of mitochondrial homeostasis, allows to perform simulation experiments so as to monitor the conformational changes, as well as the intersection of form and function.

摘要

有序的线粒体生命周期在神经退行性疾病的病理学中起关键作用。线粒体在神经元中普遍存在,因为它们要应对不断变化的能量供应需求。线粒体的形状和位置不断变化,这是其动态特性的特征,有助于一种质量控制机制。线粒体动力学的生物学研究正在揭示裂变和融合的机制,这些机制本质上决定了这些细胞器的形态和运动性。控制线粒体网络稳态是神经元正常功能的关键因素。据报道,与疾病相关的基因与线粒体功能障碍有关。越来越多的证据表明线粒体功能紊乱与神经元疾病有关,如阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩侧索硬化症(ALS)。神经退行性疾病的复杂性以及线粒体的动态特性表明,尽管在检测线粒体疾病背后的生物学方面取得了进展,但在实验室中很难确定其与这些疾病的联系。考虑到需要在空间和时间层面上对信号通路进行建模,使用多尺度建模框架存在挑战,而这对于理解复杂生物系统的动态性至关重要。使用计算模型来表示线粒体稳态的定性和定量结构,能够进行模拟实验,以监测构象变化以及形式与功能的交叉。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd40/7242057/da53e8ddcc90/neurosci-07-01-004-g001.jpg

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