| Literature DB >> 27551907 |
Ming Gao1,2, Haoqian Zhang1,2, Alpa Trivedi1,2, Kiran V Mahasenan1,2, Valerie A Schroeder1,2, William R Wolter1,2, Mark A Suckow1,2, Shahriar Mobashery1,2, Linda J Noble-Haeusslein1,2, Mayland Chang1,2.
Abstract
Matrix metalloproteinase (MMP)-2 knockout (KO) mice show impaired neurological recovery after spinal cord injury (SCI), suggesting that this proteinase is critical to recovery processes. However, this finding in the KO has been confounded by a compensatory increase in MMP-9. We synthesized the thiirane mechanism-based inhibitor ND-378 and document that it is a potent (nanomolar) and selective slow-binding inhibitor of MMP-2 that does not inhibit the closely related MMP-9 and MMP-14. ND-378 crosses the blood-spinal cord barrier, achieving therapeutic concentrations in the injured spinal cord. Spinal-cord injured mice treated with ND-378 showed no change in long-term neurological outcomes, suggesting that MMP-2 is not a key determinant of locomotor recovery.Entities:
Keywords: MMP-2; ND-378; brain distribution; spinal cord injury
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Year: 2016 PMID： 27551907 DOI： 10.1021/acschemneuro.6b00217
Source DB: PubMed Journal: ACS Chem Neurosci ISSN： 1948-7193 Impact factor: 4.418