Dudanova Irina
Molecular Neurodegeneration Group, Max Planck Institute of Neurobiology, Martinsried, Germany.
Front Mol Neurosci. 2022 Mar 8;15:829365. doi: 10.3389/fnmol.2022.829365. eCollection 2022.
Cellular health depends on the integrity and functionality of the proteome. Each cell is equipped with a protein quality control machinery that maintains protein homeostasis (proteostasis) by helping proteins adopt and keep their native structure, and ensuring the degradation of damaged proteins. Postmitotic cells such as neurons are especially vulnerable to disturbances of proteostasis. Defects of protein quality control occur in aging and have been linked to several disorders, including neurodegenerative diseases. However, the exact nature and time course of such disturbances in the context of brain diseases remain poorly understood. Sensors that allow visualization and quantitative analysis of proteostasis capacity in neurons are essential for gaining a better understanding of disease mechanisms and for testing potential therapies. Here, I provide an overview of available biosensors for assessing the functionality of the neuronal proteostasis network, point out the advantages and limitations of different sensors, and outline their potential for biological discoveries and translational applications.
细胞健康取决于蛋白质组的完整性和功能。每个细胞都配备有蛋白质质量控制机制，通过帮助蛋白质形成并保持其天然结构，以及确保受损蛋白质的降解来维持蛋白质稳态（蛋白质平衡）。诸如神经元等有丝分裂后细胞尤其容易受到蛋白质平衡紊乱的影响。蛋白质质量控制缺陷在衰老过程中出现，并与包括神经退行性疾病在内的多种疾病相关联。然而，在脑部疾病背景下，此类紊乱的确切性质和时间进程仍知之甚少。能够实现神经元蛋白质平衡能力可视化和定量分析的传感器，对于更好地理解疾病机制以及测试潜在疗法至关重要。在此，我概述了用于评估神经元蛋白质平衡网络功能的现有生物传感器，指出了不同传感器的优缺点，并概述了它们在生物学发现和转化应用方面的潜力。
