Peters Myriam, Wielsch Betty, Boltze Johannes
Department of Cell Therapy, Fraunhofer-Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany; Experimental Epilepsy Research, Department of Neurosurgery, Medical Center-University of Freiburg, 79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; BrainLinks-BrainTools, Cluster of Excellence, University of Freiburg, 79106 Freiburg, Germany.
Department of Cell Therapy, Fraunhofer-Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
Neurochem Int. 2017 Jul;107:66-77. doi: 10.1016/j.neuint.2017.03.011. Epub 2017 Mar 18.
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism. However, the detailed roles of SUMOylation during CNS hypoxia-ischemia are not well understood so far. Moreover, SUMOylation is subjected to complex regulatory mechanisms and might exert protective, but also detrimental processes during hypoxic-ischemic stress. This review provides a comprehensive overview on SUMOylation processes under physiological and pathological conditions in the CNS. A particular spotlight is set on clinically relevant hypoxic-ischemic conditions such as stroke by focusing on peri- and postischemic SUMOylation in neurons and astrocytes. The review describes relevant SUMOylation targets in these cells to discuss confirmed and supposed downstream mechanisms potentially contributing to neuroprotection, but also to sometimes detrimental processes. The review further provides unique insights into the time course of SUMO responses during cerebral ischemia in different cerebral cell populations. This includes neurons, astrocytes, but also phagocytes that become activated (microglia) and/or migrate (macrophages/monocytes) to the ischemic CNS. Based on this compact knowledge, the review finally suggests potential directions for future basic and translational research.
通过添加或去除小泛素样修饰物（SUMO）蛋白来修饰蛋白质的过程，即SUMO化，有助于调节真核细胞中的众多过程。SUMO化也是对不同形式代谢应激的关键反应和适应机制。中枢神经系统（CNS），尤其是神经元，由于缺乏大量的氧气和能量储备，对缺氧缺血应激高度敏感。在大脑对代谢应激的许多分子反应中都观察到了SUMO化，因此被认为是一种内源性神经保护机制。然而，到目前为止，SUMO化在中枢神经系统缺氧缺血过程中的详细作用尚未完全了解。此外，SUMO化受到复杂的调控机制影响，在缺氧缺血应激期间可能发挥保护作用，但也可能产生有害作用。本综述全面概述了中枢神经系统在生理和病理条件下的SUMO化过程。通过关注神经元和星形胶质细胞缺血周围和缺血后的SUMO化，特别聚焦于临床上相关的缺氧缺血情况，如中风。该综述描述了这些细胞中的相关SUMO化靶点，以讨论已证实的和推测的潜在下游机制，这些机制可能有助于神经保护，但有时也会导致有害过程。该综述还进一步深入探讨了不同脑细胞群体在脑缺血期间SUMO反应的时间进程。这包括神经元、星形胶质细胞，还有被激活（小胶质细胞）和/或迁移（巨噬细胞/单核细胞）到缺血性中枢神经系统的吞噬细胞。基于这些紧凑的知识，该综述最后提出了未来基础研究和转化研究的潜在方向。
