Andries Lien, Van Hove Inge, Moons Lieve, De Groef Lies
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
Laboratory of Ophthalmology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Mol Neurobiol. 2017 Apr;54(3):2114-2125. doi: 10.1007/s12035-016-9801-x. Epub 2016 Feb 29.
By proteolytic cleavage, matrix metalloproteinases (MMPs) not only remodel the extracellular matrix (ECM) but they also modify the structure and activity of other proteinases, growth factors, signaling molecules, cell surface receptors, etc. Their vast substrate repertoire adds a complex extra dimension of biological control and turns MMPs into important regulatory nodes in the protease web. In the central nervous system (CNS), the detrimental impact of elevated MMP activities has been well-described for traumatic injuries and many neurodegenerative diseases. Nonetheless, there is ample proof corroborating MMPs as fine regulators of CNS physiology, and well-balanced MMP activity is instrumental to development, plasticity, and repair. In this manuscript, we review the emerging evidence for MMPs as beneficial modulators of axonal regeneration in the mammalian CNS. By exploring the multifactorial causes underlying the inability of mature axons to regenerate, and describing how MMPs can help to overcome these hurdles, we emphasize the benign actions of these Janus-faced proteases.
通过蛋白水解切割，基质金属蛋白酶（MMPs）不仅能重塑细胞外基质（ECM），还能改变其他蛋白酶、生长因子、信号分子、细胞表面受体等的结构和活性。它们广泛的底物谱增加了生物控制的复杂额外维度，并使MMPs成为蛋白酶网络中的重要调控节点。在中枢神经系统（CNS）中，MMP活性升高对创伤性损伤和许多神经退行性疾病的有害影响已得到充分描述。尽管如此，有充分证据证实MMPs是CNS生理学的精细调节因子，且平衡良好的MMP活性对发育、可塑性和修复至关重要。在本手稿中，我们综述了MMPs作为哺乳动物CNS轴突再生有益调节因子的新证据。通过探究成熟轴突无法再生的多因素原因，并描述MMPs如何有助于克服这些障碍，我们强调了这些双面蛋白酶的良性作用。
