Department of Clinical Genetics, Amsterdam University Medical Centers location VUmc, 1081 HV Amsterdam, The Netherlands.
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit (VU), 1081 HV Amsterdam, The Netherlands.
Biomolecules. 2020 Jul 22;10(8):1090. doi: 10.3390/biom10081090.
Neurons are highly specialized cells that continuously and extensively communicate with other neurons, as well as glia cells. During their long lifetime, the post-mitotic neurons encounter many stressful situations that can disrupt protein homeostasis (proteostasis). The importance of tight protein quality control is illustrated by neurodegenerative disorders where disturbed neuronal proteostasis causes neuronal dysfunction and loss. For their unique function, neurons require regulated and long-distance transport of membrane-bound cargo and organelles. This highlights the importance of protein quality control in the neuronal endomembrane system, to which the unfolded protein response (UPR) is instrumental. The UPR is a highly conserved stress response that is present in all eukaryotes. However, recent studies demonstrate the existence of cell-type-specific aspects of the UPR, as well as cell non-autonomous UPR signaling. Here we discuss these novel insights in view of the complex cellular architecture of the brain and the implications for neurodegenerative diseases.
神经元是高度特化的细胞，它们与其他神经元以及神经胶质细胞持续广泛地进行交流。在其漫长的生命周期中，有丝分裂后的神经元会遇到许多应激情况，这些情况会破坏蛋白质的内稳态（蛋白质平衡）。神经退行性疾病中神经元蛋白质平衡紊乱导致神经元功能障碍和丧失，这说明了严格的蛋白质质量控制的重要性。由于神经元具有独特的功能，它们需要对膜结合货物和细胞器进行调节和长距离运输。这凸显了蛋白质质量控制在神经元内膜系统中的重要性，未折叠蛋白反应（UPR）对此至关重要。UPR 是一种高度保守的应激反应，存在于所有真核生物中。然而，最近的研究表明，UPR 存在细胞类型特异性方面，以及非自主细胞的 UPR 信号。在这里，我们根据大脑复杂的细胞结构以及对神经退行性疾病的影响来讨论这些新的见解。
