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.
|Number of pages||6|
|Journal||ACS Chemical Neuroscience|
|State||Published - Nov 16 2016|
Bibliographical noteFunding Information:
We thank Sandra Canchola and the Neurobehavioral Core for Rehabilitation Research at UCSF for providing the facilities to conduct the behavioral analyses.
© 2016 American Chemical Society.
Copyright 2017 Elsevier B.V., All rights reserved.
- brain distribution
- spinal cord injury
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cell Biology