Gottschall Paul E, Howell Matthew D
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States.
Matrix Biol. 2015 May-Jul;44-46:70-6. doi: 10.1016/j.matbio.2015.01.014. Epub 2015 Jan 24.
The components of the adult extracellular matrix in the central nervous system form a lattice-like structure that is deposited as perineuronal nets, around axon initial segments and as synapse-associated matrix. An abundant component of this matrix is the lecticans, chondroitin sulfate-bearing proteoglycans that are the major substrate for several members of the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) family. Since lecticans are key regulators of neural plasticity, ADAMTS cleavage of lecticans would likely also contribute to neuroplasticity. Indeed, many studies have examined the neuroplastic contribution of the ADAMTSs to damage and recovery after injury and in central nervous system disease. Much of this data supports a role for the ADAMTSs in recovery and repair following spinal cord injury by stimulating axonal outgrowth after degradation of a glial scar and improving synaptic plasticity following seizure-induced neural damage in the brain. The action of the ADAMTSs in chronic diseases of the central nervous system appears to be more complex and less well-defined. Increasing evidence indicates that lecticans participate in synaptic plasticity in neurodegenerative disease states. It will be interesting to examine how ADAMTS expression and action would affect the progression of these diseases.
中枢神经系统中成年细胞外基质的成分形成一种晶格状结构，该结构以神经周网的形式沉积在轴突起始段周围，并作为突触相关基质。这种基质的一种丰富成分是凝集素，即带有硫酸软骨素的蛋白聚糖，它是ADAMTSs（具有血小板反应蛋白基序的解整合素和金属蛋白酶）家族多个成员的主要底物。由于凝集素是神经可塑性的关键调节因子，ADAMTSs对凝集素的切割可能也有助于神经可塑性。事实上，许多研究已经探讨了ADAMTSs在损伤后以及中枢神经系统疾病中对损伤和恢复的神经可塑性贡献。这些数据大多支持ADAMTSs在脊髓损伤后的恢复和修复中发挥作用，即通过在胶质瘢痕降解后刺激轴突生长，以及在癫痫诱导的脑神经元损伤后改善突触可塑性。ADAMTSs在中枢神经系统慢性疾病中的作用似乎更为复杂且定义不明确。越来越多的证据表明，凝集素参与神经退行性疾病状态下的突触可塑性调节。研究ADAMTSs的表达和作用如何影响这些疾病的进展将很有意思。
