Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

Table 3

Overview of in vitro and in vivo MMP inhibitor studies in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis.

Neurodegenerative disease	Type of MMP inhibitor	Inhibitor	Phenotype	Model system/Source	References
Alzheimer’s disease	Broad spectrum	GM6001	Increased brain interstitial fluid Aβ levels	Transgenic mice overexpressing the Swedish variant of APP	[85]
	Broad spectrum	GM6001	Protection from BBB permeability	In vitro (brain endothelial cells)	[33]
	Broad spectrum	GM6001	Protection from BCSFB permeability	In vivo (icv injection with Aβ oligomers)	[32]
	Broad spectrum	GM6001	Reduced oxidative stress	Transgenic mouse model of AD	[86]
Parkinson’s disease	Selective	NNGH (N-isobutyl-N-[4-methoxyphenylsulfonyl]-glycylhydroxamic acid)	Decrease of TNF release from microglial cells and increased cell survival	In vitro (mouse mesencephalic cells)	[51]
Multiple sclerosis	Broad spectrum	GM6001	Reversal of clinical signs of EAE	EAE	[87]
			Reduced α4 integrin-mediated transmigration	EAE	[88]
			Reversed clinical symptoms and reduced MMP-9 activity	SJL/J mice	[89]
	Broad spectrum	RO31-9790	Reduced clinical severity of adoptively transferred EAE	EAE	[90]
	Broad spectrum	UK221,316	Reduced α4 integrin-mediated transmigration and EAE	EAE	[88]
	Broad spectrum	d-pencillamine	Reduced mortality and morbidity rates	EAE	[91]
	Broad spectrum	BB1101	Reduces clinical signs and weight loss in an acute EAE	Lewis rats	[92]
	Broad spectrum	Minocycline	Reduced activity and the expression of MMP-9 in T-cells	EAE	[93]
			Inhibits MMP-2	EAE	[94]
		α-lipoic acid	Reduced infiltration of T-cells and reduced MMP-9 activity	EAE	[95]

Aβ, β amyloid; AD, Alzheimer’s disease; BBB, blood-brain barrier; BCSFB, blood-CSF barrier; CSF, cerebrospinal fluid; EAE, Experimental autoimmune encephalomyelitis; MMP, matrix metalloproteinase; TNF, tumor necrosis factor.