Table 1:

Some important matrix metalloproteinases in the central nervous system and their relationship with the pathogenesis of multiple sclerosis

MMP	MW in kDa		Cell source	Functions	TIMPs
	Pro-enzyme	Active form
MMP-1	57 and 52	42	Astrocytes, monocytes, macrophages and microglia	Unknown Activator for MMP-2 and -9 Breaks down the interstitial collagens (types I, II and III)	TIMP-1
MMP-2	72	63	Astrocytes, microglia, monocytes, macrophages and endothelial cells	BBB disruption, which facilitates immune cell transmigration into the CNS Fragmentation of the MBP Demyelination Axonal injury Activator for MMP-1 and -9	TIMP-2 and TIMP-4
MMP-3	57	54	Astrocytes, monocytes, macrophages, endothelial cells and microglia	BBB disruption Activates microglia or ‘white matter’ brain cells Activator for MMP-1, -7 and -9 Normal functioning as neuronal migration Neurite outgrowth and CNS development Stem cell migration Neuroprotection Remyelination in the injured CNS	TIMP-1 and TIMP-3
MMP-7	29	20	Microglia, monocytes and macrophages	Cleaves NR1 (an obligate sub-unit of the NMDA receptor) Activator for MMP-1, -2 and -9	TIMP-1
MMP-9	92	67	Astrocytes, microglia, monocytes, macrophages, endothelial cells, neurons, neutrophils and CCR2+ CCR5+ T cells	Increases the permeability of the BBB Facilitates the infiltration of leukocytes into the CNS Myelin sheath degradation Neuronal damage	TIMP-1
MMP-12	∼54	48	Macrophages, microglia and astrocytes	Unknown Potentially partakes in myelinogenesis	TIMP-1
MMP-14	66	∼54	Monocytes	Activator for MMP-2 Receptor for TIMP-2 and/or the pro-MMP-2/TIMP-2 complex	TIMP-2 and TIMP-4

MMP = matrix metalloproteinase; MW = molecular weight; kDa = kilodaltons; TIMP = tissue inhibitors of metalloproteinases; BBB = blood-brain barrier; CNS = central nervous system; MBP = myelin basic protein; NMDA = N-methyl-d-aspartate.