Josefson Rebecca, Andersson Rebecca, Nyström Thomas
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden
Essays Biochem. 2017 Jul 11;61(3):317-324. doi: 10.1042/EBC20160085. Print 2017 Jul 15.
Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases. PQC consists of two interrelated systems: the temporal control system aimed at refolding, repairing, and/or removing aberrant proteins and their aggregates and the spatial control system aimed at harnessing the potential toxicity of aberrant proteins by sequestering them at specific cellular locations. The accumulation of toxic conformers of aberrant proteins during ageing is often declared to be a consequence of an incapacitated temporal PQC system-i.e. a gradual decline in the activity of chaperones and proteases. Here, we review the current knowledge on PQC in relation to ageing and highlight that the breakdown of both temporal and spatial PQC may contribute to ageing and thus comprise potential targets for therapeutic interventions of the ageing process.
衰老可以定义为细胞和身体功能的逐渐衰退，同时伴随着对环境的敏感性增加和死亡风险上升。死亡率上升与所谓衰老因子在细胞内逐渐积累存在因果关联，受损和聚集的蛋白质被认为是其中之一。这类聚集蛋白还会引发多种与年龄相关的神经退行性疾病，如阿尔茨海默病、帕金森病和亨廷顿舞蹈症，凸显了蛋白质质量控制（PQC）在衰老及其相关疾病中的重要性。PQC由两个相互关联的系统组成：旨在重新折叠、修复和/或清除异常蛋白质及其聚集体的时间控制系统，以及旨在通过将异常蛋白质隔离在特定细胞位置来控制其潜在毒性的空间控制系统。衰老过程中异常蛋白质毒性构象的积累通常被认为是时间PQC系统功能丧失的结果，即伴侣蛋白和蛋白酶的活性逐渐下降。在此，我们回顾了与衰老相关的PQC的现有知识，并强调时间和空间PQC的崩溃都可能导致衰老，因此可能成为衰老过程治疗干预的潜在靶点。
