Neurodegeneration and regeneration.
Neurodegeneration and regeneration.
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神经变性和再生。
DOI：
10.1002/jnr.24069
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发表时间：
2017
影响因子：
4.2
通讯作者：
Niu,Jingwen
中科院分区：
文献类型：
--
作者：
Niu,Jingwen
成年哺乳动物的中枢神经系统（CNS）和周围神经系统（PNS）的主要区别之一是再生能力。长期以来，人们一直认为中枢神经系统的神经元在损伤后不会再生。正如卡哈尔的信条所描述的那样，“一旦发育结束，轴突和树突的生长和再生之源就会不可逆转地枯竭。”在成人中枢，神经通路是固定的、终结的、不可改变的。一切都可能死亡。没有什么可以再生”（Ramón y Cajal, 1969）。然而，近几十年来的深入研究表明，受损的中枢神经系统轴突在操纵内外因素后可以恢复其生长能力。揭示这一现象背后的机制将极大地推动神经变性和再生领域以及治疗方法的发展。与再生良好的周围神经不同，中枢神经系统轴突在损伤后总是不能再生，导致永久性功能缺陷。研究人员和医生都知道，组织和器官在受伤或病理状态下会以多种方式发生变化。损伤后，神经胶质细胞和免疫反应诱导瘢痕组织的形成改变了局部解剖结构（Brosius Lutz and Barres, 2014; Silver et al., 2014）。作为防止剧烈炎症和保护剩余脆弱组织的物理和分子壁，疤痕是脑和脊髓损伤后伤口愈合的重要组成部分（Silver和Miller， 2004）。疤痕壁的星形胶质成分是通过一系列步骤形成的：(a)星形胶质细胞的快速迁移（Fitch and Silver, 1997; George and Griffin, 1994），(b)位于病变边缘的反应性星形胶质细胞（胶质形成）的增殖（Aldskogius and Kozlova, 1998; Bush et al., 1999; Wanner et al., 2013），(c)反应性星形胶质细胞分泌的中间丝蛋白（主要是胶质纤维酸性蛋白[GFAP]）的积累(Bardehle et al., 2013；Liuzzi and Lasek, 1987；Pekny等人，1999),(d)胶质层重组成网状包膜（Bardehle等人，2013；Wanner等人，2013），以及(e)各种细胞外基质（ECM）分子的产生（Busch和Silver, 2007; Yamaguchi, 2000）。胶质包膜的物理壁被认为是一个不支持再生轴突克服的环境。GFAP的表达和ECM蛋白（包括硫酸软骨素蛋白聚糖（CSPGs））的上调与损伤区域的再生失败有关（Filous et al., 2010; Yiu and He, 2006）。因此，它是
One of the main differences between the adult mammalian’s central nervous system (CNS) and peripheral nervous systems (PNS) is the capability to regenerate. It has long been thought that neurons in the CNS do not regenerate after injury. As depicted in Cajal’s dogma,“Once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed, ended, and immutable. Everything may die. Nothing may be regenerated”(Ramón y Cajal, 1969). Yet, intensive studies over the past few decades have revealed that injured CNS axons can regain their growth ability after manipulating intrinsic and extrinsic factors. Unraveling the mechanisms underlying this phenomenon will greatly advance the neurodegeneration and regeneration field and the development of therapeutic methods.Unlike the well-regenerating peripheral nerves, CNS axons invariably fail to regenerate after injury, resulting in permanent functional deficits. Researchers and physicians understand that tissues and organs change in many ways after injury or during pathological conditions. After an injury, the formation of scar tissue induced by glia cells and immune response, alters the local anatomical structure (Brosius Lutz and Barres, 2014; Silver et al., 2014). As a physical and molecular wall used to prevent intense inflammation and protect remaining fragile tissue, the scar is an essential part of wound healing after brain and spinal cord injuries (Silver and Miller, 2004). The astroglial component of the scar wall is formed by serial steps:(a) the rapid migration of astrocytes (Fitch and Silver, 1997; George and Griffin, 1994),(b) the proliferation of reactive astrocytes (gliosis) that reside at the lesion margin (Aldskogius and Kozlova, 1998; Bush et al., 1999; Wanner et al., 2013),(c) the accumulation of intermediate filament proteins (predominantly glial fibrillary acidic protein [GFAP]) secreted by reactive astrocytes (Bardehle et al., 2013; Liuzzi and Lasek, 1987; Pekny et al., 1999),(d) the restructuring of the gliotic layer into a mesh-like envelope (Bardehle et al., 2013; Wanner et al., 2013), and (e) the production of a variety of extracellular matrix (ECM) molecules (Busch and Silver, 2007; Yamaguchi, 2000). The physical wall of the gliotic envelope has been considered an unsupportive environment for regenerating axons to overcome. The expression of GFAP, and the upregulation of ECM proteins, including chondroitin sulfate proteoglycans (CSPGs), which are associated with regeneration failure in the injured area (Filous et al., 2010; Yiu and He, 2006). Thus, it is