Differing and temporally specific roles of different MMPs after CNS injury, along with the implication of MMPs in neuropathic pain states following spinal cord injury means the premise of broad spectrum MMP alteration warrants natural caution. Although it may be noted that the synthetic tetracycline derivative minocycline has weak broad-spectrum MMP inhibitory activity and, alongside safety, reports a nonsignificant trend towards improved neurological
and functional recovery following a phase II clinical trial as a therapeutic for spinal check details cord injury (http://www.clinicaltrials.gov/SHOW/NCT00559494), . In addition, MMP substrates are extremely wide-ranging and many are highly
nonspecific. https://www.selleckchem.com/HSP-90.html As an example, while MMP-3 degrades candidate CSPGs upregulated after CNS injury, it also degrades collagen types II, III, IV, IX and X, fibronectin, laminin and elastin and activates other MMPs including MMP-1, MMP-7 and the pro-inflammatory MMP-9. In addition there is redundancy; aggrecan, as an example, is cleaved by MMP-1, -2, -3, -7, -8, -9, -11, -13, -14, -15, -19, -20 . Due to broad specificity and wide-ranging orchestrated and inter-regulatory roles of MMPs, attention is also drawn to other, more specific, endogenous matrix remodelling enzymes. MMPs belong to the metzincin superfamily of metalloproteinases, also including astacins, ADAMs (a protein with a disintegrin and metalloprotease domain) and ADAM-TS (an ADAM with a thrombospondin-like motif) proteases. Of
particular interest, ADAMTS-4 reverses the proteoglycan-mediated inhibition of neurite outgrowth in vitro  and in vivo, ADAMTS-4 has been shown to promote functional recovery after moderate thoracic contusion in the rat when delivered intrathecally via osmotic mini-pump ; interestingly, functional improvement was Beta adrenergic receptor kinase of the same magnitude to that seen with the more commonly used enzyme chondroitinase (the use of chondroitinase as a tool to promote repair following CNS injury will be discussed below). With increasing specificity in terms of proteolytic target, a recent study reports use of the mammalian enzyme arylsulphatase B (ARSB) (N-acetylgalactosamine 4-sulphatase) which removes the C-4-S moieties from CSPGs, previously reported to be inhibitory to neuronal growth . Following moderate and severe thoracic spinal compression injuries in the mouse, a single intraspinal injection of human ARSB removed immunoreactivity for C-4-S which was associated with increased serotonergic and tyrosine hydroylase positive axon sprouting and functional locomotor recovery . The authors suggest that ARSB has interesting advantages in that its enzymatic activity is optimal at acidic pH and the CNS injury environment has been reported to display mild acidosis .