Satapathy Sandeep, Wilson Mark R
Blavatnik Institute of Cell Biology, Harvard Medical School, Boston; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Molecular Horizons and The School of Chemistry and Molecular Bioscience, University of Wollongong; Illawarra Health and Medical Research Institute, Northfields Avenue, Wollongong, NSW, Australia.
Neural Regen Res. 2023 Apr;18(4):769-772. doi: 10.4103/1673-5374.353483.
Protein quality control involves many processes that jointly act to regulate the expression, localization, turnover, and degradation of proteins, and has been highlighted in recent studies as critical to the differentiation of stem cells during regeneration. The roles of constitutively secreted extracellular chaperones in neuronal injury and disease are poorly understood. Extracellular chaperones are multifunctional proteins expressed by many cell types, including those of the nervous system, known to facilitate protein quality control processes. These molecules exert pleiotropic effects and have been implicated as playing important protective roles in a variety of stress conditions, including tissue damage, infections, and local tissue inflammation. This article aims to provide a critical review of what is currently known about the functions of extracellular chaperones in neuronal repair and regeneration and highlight future directions for this important research area. We review what is known of four constitutively secreted extracellular chaperones directly implicated in processes of neuronal damage and repair, including transthyretin, clusterin, α2-macroglobulin, and neuroserpin, and propose that investigation into the effects of these and other extracellular chaperones on neuronal repair and regeneration has the potential to yield valuable new therapies.
蛋白质质量控制涉及许多共同作用以调节蛋白质表达、定位、周转和降解的过程，并且在最近的研究中被强调为再生过程中干细胞分化的关键因素。组成型分泌的细胞外伴侣蛋白在神经元损伤和疾病中的作用尚不清楚。细胞外伴侣蛋白是由包括神经系统细胞类型在内的多种细胞类型表达的多功能蛋白质，已知其有助于蛋白质质量控制过程。这些分子具有多效性作用，并被认为在包括组织损伤、感染和局部组织炎症在内的各种应激条件下发挥重要的保护作用。本文旨在对目前已知的细胞外伴侣蛋白在神经元修复和再生中的功能进行批判性综述，并突出这一重要研究领域的未来方向。我们综述了已知直接参与神经元损伤和修复过程的四种组成型分泌的细胞外伴侣蛋白，包括甲状腺素运载蛋白、簇集素、α2-巨球蛋白和神经丝氨酸蛋白酶抑制剂，并提出对这些以及其他细胞外伴侣蛋白对神经元修复和再生影响的研究有可能产生有价值的新疗法。
