Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronan is a component of the extracellular matrix of the central nervous system, and forms perineuronal nets around neurons. It has been recently reported that the hyaluronan-degrading enzyme hyaluronidase promotes lateral mobility of AMPA-type glutamate receptors and enhances synaptic plasticity. However, the biological significance of hyaluronan-degrading products (oligosaccharides) has not been studied in depth. Here we investigated the effects of hyaluronan oligosaccharides on motor function recovery after spinal cord injury in rats. The disaccharide HA2 and especially the tetrasaccharide HA4, significantly improved motor function, unlike the case with oligosaccharides composed of 6-12 saccharides. Consistent with this finding, HA4 treatment enhanced axonal regeneration/sprouting, as assessed by corticospinal tract tracer fiber counts. HA4 treatment also significantly suppressed accumulation of Iba-1-positive cells in a lesion two weeks after injury. In vitro experiments demonstrated that NMDA-induced neuronal cell death was partly blocked by HA4, but not by other oligosaccharides, whereas proteoglycan-mediated inhibition of neurite outgrowth was not affected by treatment with any oligosaccharide examined. Taken together, the present results revealed that due in part to its neuroprotective activity, HA4 promotes motor function recovery after spinal cord injury.
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PMID:Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats. 2111 Oct 28

Long-term potentiation (LTP) is widely perceived as a memory substrate and in the hippocampal CA3-CA1 pathway, distinct forms of LTP depend on NMDA receptors (nmdaLTP) or L-type voltage-gated calcium channels (vdccLTP). LTP is also known to be effectively regulated by extracellular proteolysis that is mediated by various enzymes. Herein, we investigated whether in mice hippocampal slices these distinct forms of LTP are specifically regulated by different metalloproteinases (MMPs). We found that MMP-3 inhibition or knock-out impaired late-phase LTP in the CA3-CA1 pathway. Interestingly, late-phase LTP was also decreased by MMP-9 blockade. When both MMP-3 and MMP-9 were inhibited, both early- and late-phase LTP was impaired. Using immunoblotting, in situ zymography, and immunofluorescence, we found that LTP induction was associated with an increase in MMP-3 expression and activity in CA1 stratum radiatum. MMP-3 inhibition and knock-out prevented the induction of vdccLTP, with no effect on nmdaLTP. L-type channel-dependent LTP is known to be impaired by hyaluronic acid digestion. We found that slice treatment with hyaluronidase occluded the effect of MMP-3 blockade on LTP, further confirming a critical role for MMP-3 in this form of LTP. In contrast to the CA3-CA1 pathway, LTP in the mossy fiber-CA3 projection did not depend on MMP-3, indicating the pathway specificity of the actions of MMPs. Overall, our study indicates that the activation of perisynaptic MMP-3 supports L-type channel-dependent LTP in the CA1 region, whereas nmdaLTP depends solely on MMP-9.
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PMID:Mechanisms of NMDA Receptor- and Voltage-Gated L-Type Calcium Channel-Dependent Hippocampal LTP Critically Rely on Proteolysis That Is Mediated by Distinct Metalloproteinases. 2806 22