Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, 39120 Magdeburg, Germany.
Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, 39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), 39120 Magdeburg, Germany; Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Brain Res Bull. 2018 Jan;136:101-108. doi: 10.1016/j.brainresbull.2017.03.003. Epub 2017 Mar 8.
Extracellular matrix (ECM) molecules in the central nervous system form highly organized ECM structures around cell somata, axon initial segments, and synapses and play prominent roles in early development by guiding cell migration, neurite outgrowth and synaptogenesis, and by regulating closure of the critical period of development, synaptic plasticity and stability, cognitive flexibility, and axonal regeneration in adults. Major components of neural ECM, including chondroitin sulfate proteoglycans (CSPGs), tenascin-R and hyaluronic acid, are synthesized by both neurons and glial cells. The expression of these molecules is dynamically regulated during brain development in physiological conditions, shaping both neuronal and glial functions through multitude of molecular mechanisms. Upregulation of particular CSPGs and other ECM molecules, in particular by reactive astrocytes, after CNS injuries, during aging, neuroinflammation, and neurodegeneration on the one hand results in formation of growth-impermissive environment and impaired synaptic plasticity. On the other hand, ECM appeared to have a neuroprotective effect, at least in the form of perineuronal nets. CSPGs-degrading matrix metalloproteinases (MMPs) and several members of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family of proteases are secreted by neurons and glia and may drive neural ECM remodeling in physiological conditions as well as after brain injury and other brain disorders. Thus, targeting expression of specific ECM molecules, associated glycans and degrading enzymes may lead to development of new therapeutic strategies promoting regeneration and synaptic plasticity.
中枢神经系统的细胞外基质 (ECM) 分子围绕细胞体、轴突起始段和突触形成高度组织化的 ECM 结构，并在早期发育中发挥重要作用，通过指导细胞迁移、轴突生长和突触发生，以及调节发育关键期的关闭、突触可塑性和稳定性、认知灵活性和成年期轴突再生。神经 ECM 的主要成分，包括软骨素硫酸盐蛋白聚糖 (CSPGs)、 tenascin-R 和透明质酸，由神经元和神经胶质细胞共同合成。在生理条件下，这些分子的表达在大脑发育过程中是动态调节的，通过多种分子机制塑造神经元和神经胶质细胞的功能。中枢神经系统损伤后、衰老时、神经炎症和神经退行性变期间，特定 CSPGs 和其他 ECM 分子（特别是反应性星形胶质细胞）的上调一方面导致形成生长抑制环境和突触可塑性受损。另一方面，ECM 似乎具有神经保护作用，至少以神经周细胞网络的形式存在。细胞外基质金属蛋白酶 (MMPs) 和整合素金属蛋白酶与血小板反应蛋白基序 (ADAMTS) 家族蛋白酶的几个成员由神经元和神经胶质细胞分泌，可能在生理条件以及脑损伤和其他脑疾病后驱动神经 ECM 重塑。因此，靶向特定 ECM 分子、相关聚糖和降解酶的表达可能会导致开发新的治疗策略，促进再生和突触可塑性。
