Table 1.
The role of MMPs in neurodegenerative diseases.
| MMPs Involved/ Neurodegenerative Disease |
Model System | Role of MMPs | Ref. |
|---|---|---|---|
| MMP-2/PD | In vitro (PC12 cells) | Activates microglia | [97] |
| Patients | Detected in microglia and astrocytes | [99] | |
| In vitro (neuron-glia culture) | Induces DAergic neuronal death in culture of glia-neuron (mesencephalic) | [103] | |
| MMP-2/AD | In vivo (rats) | Involved in synaptic plasticity | [199] |
| In-vitro (microglial cell line) | Increased microglial expression after Aβ oligomer stimulation | [133] | |
| MMP-1/AD | In vitro (primary astrocytes) | Low MMP-9 levels and decreased MMP-2 activity after Aβ oligomer stimulation. | [139] |
| Patients | Increased MMP-1 levels in AD patients | [200,201] | |
| MMP-3/PD | In vitro (primary cultured DAergic neurons) | MMP-3 neuronal secretion | [102] |
| In vitro (primary mesencephalic cultures) | Induces NO production in microglia | [98,100] | |
| In vitro (human DAergic neuroblastoma) | α-synuclein proteolysis | [202] | |
| MMP-3/AD | Patients | Significant upregulation of MMP-3 plasma levels | [138] |
| In vivo (icv injections of Aβ oligomer) | Increased MMP-3 expression | [52] | |
| In vitro (APP-CHO cells) | Ability to degrade Aβ | [203] | |
| In vivo (icv injection of Aβ oligomer) | Enhanced permeability of BCSFB | [52] | |
| MMP-2/ALS | Patients | Increased permeability of BBB | [204] |
| Patients (serum) | To evaluate ALS progression | [161] | |
| MMP-9/AD | In vitro (astrocytes) | Detected in astrocytes when treated with fibrillar and soluble Aβ | [205] |
| In vivo (rats) | Involved in synaptic plasticity | [199] | |
| In vivo (mice) | Increased levels in hippocampus on icv injection | [132] | |
| Patients (CSF) | Activation of MMP-9/CypA in pericytes, BBB disruption | [137] | |
| In vitro (isolates from brain of patients) | Cleavage of Aβ1-40 by MMP-9 | [206] | |
| MMP-3/ALS | In vivo (G93A SOD1 mice) | Upregulation of neuronal FasL and TNF | [157] |
| In vivo (mutant SOD1 transgenic mice) | Dysregulated MMP-3 activity with ALS progression | [165] | |
| In vivo (G93A SOD1 mice) | Encourages motor cell death in neurons | [165] | |
| MMP-1/MS | Patients (monocytes) | Increased mRNA levels of MMP-1 | [182] |
| Patients (postmortem brain samples) | Weak astrocytic expression | [207] | |
| MMP-3/MS | Patients (monocytes) | Increased mRNA levels of MMP-3 | [182] |
| Patients (postmortem brain samples) | Expression in endothelial cells | [207] | |
| MMP-9/HD | In vivo (3-nitropropionic acid animal disease model) | Increased expression of MMP-9 | [195] |
| MMP-9/PD | Patients (postmortem brain tissues) | Increased expression of MMP-9 in SN | [116] |
| In vivo (MPTP induced PD in monkey and mouse model) | Primary localization of MMP-9 in neurons | [103] | |
| MMP-7/MS | Patients (monocytes) | Increased mRNA levels of MMP-7 | [182] |
| Patients (postmortem brain samples) | Secreted by blood vessels | [179] | |
| MMP-9/ALS | Patients (CSF and skin) Patients (CSF) |
Elevated in CSF and skin Low CSF levels of MMP-9 |
[160,161] |
| Patients (serum) | MMP-9 as marker distinguishing between healthy individuals and ALS | [204] | |
| MMP-10/HD | In vitro (striatal cell culture) | Cleaves huntingtin | [181] |
| MMP-9/MS | Patients (CSF samples) | Secreted by macrophages and T-cells, leads to damage of tissue | [160] |
| Patients (serum) | Increased serum levels together with TIMP-1 and -2 | [173] | |
| MMP-14/HD | In vitro (striatal cell culture) | MMP-14 knockdown reduces toxicity | [181] |
| MMP-12/AD | In vitro (microglial cell line) | Increase in microglia | [126] |
| MMP-23/HD | In vitro (striatal cell line) | MMP-23 knockdown reduces toxicity | [193] |
| MMP-13/AD | In vitro (microglial cell line) | Increase in microglia | [126] |
Aβ, β-amyloid; AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; APP, amyloid precursor protein; BBB, blood-brain barrier; BCSFB, blood-CSF barrier; CSF, cerebrospinal fluid; Cyp A, cyclophilin A; Dopaminergic, DAergic; FasL, Fas ligand; G93A SOD1 mice, transgenic mice form; HD, Huntington’s disease; i.c.v., intracerebroventricular; MMP, matrix metalloproteinase; MPTP, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine; MS, multiple sclerosis; NO, nitric oxide; PC12 cells, classical neuronal model; PD, Parkinson’s disease; SOD, superoxide dismutase; TIMP, tissue inhibitor of metalloproteinases; TNF, tumor necrosis factor.