Stawarski Michal, Stefaniuk Marzena, Wlodarczyk Jakub
Laboratory of Cell Biophysics, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Warsaw, Mazowieckie, Poland.
Laboratory of Neurobiology, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Warsaw, Mzowieckie, Poland.
Front Neuroanat. 2014 Jul 10;8:68. doi: 10.3389/fnana.2014.00068. eCollection 2014.
Dendritic spines are the locus for excitatory synaptic transmission in the brain and thus play a major role in neuronal plasticity. The ability to alter synaptic connections includes volumetric changes in dendritic spines that are driven by scaffolds created by the extracellular matrix (ECM). Here, we review the effects of the proteolytic activity of ECM proteases in physiological and pathological structural plasticity. We use matrix metalloproteinase-9 (MMP-9) as an example of an ECM modifier that has recently emerged as a key molecule in regulating the morphology and dysmorphology of dendritic spines that underlie synaptic plasticity and neurological disorders, respectively. We summarize the influence of MMP-9 on the dynamic remodeling of the ECM via the cleavage of extracellular substrates. We discuss its role in the formation, modification, and maintenance of dendritic spines in learning and memory. Finally, we review research that implicates MMP-9 in aberrant synaptic plasticity and spine dysmorphology in neurological disorders, with a focus on morphological abnormalities of dendritic protrusions that are associated with epilepsy.
树突棘是大脑中兴奋性突触传递的位点,因此在神经元可塑性中发挥着重要作用。改变突触连接的能力包括树突棘的体积变化,这是由细胞外基质(ECM)产生的支架驱动的。在这里,我们综述了ECM蛋白酶的蛋白水解活性在生理和病理结构可塑性中的作用。我们以基质金属蛋白酶-9(MMP-9)为例,它是一种ECM修饰因子,最近已成为分别调节突触可塑性和神经疾病基础的树突棘形态和畸形的关键分子。我们总结了MMP-9通过切割细胞外底物对ECM动态重塑的影响。我们讨论了它在学习和记忆中树突棘的形成、修饰和维持中的作用。最后,我们综述了涉及MMP-9在神经疾病中异常突触可塑性和树突棘畸形的研究,重点是与癫痫相关的树突突起形态异常。