|
| Neurodegenerative disease | MMPs involved | Role of MMPs | Model system | Reference |
|
| Alzheimer’s disease | MMP-1 | Increased in AD patients | Patients | [42] |
| MMP-2 | Decreased MMP-2 activity and low MMP-9 levels after stimulation with Aβ oligomers | In vitro (primary astrocytes) | [43] |
| Increased MMP-2 and proinflammatory cytokine levels in the brain | In vivo (APP/PS1 mice) | [43] |
| Induced upon interaction of Aβ and RAGE | In vitro (brain endothelial cells) | [44] |
| MMP-2 and MT1-MMP expression observed in reactive astrocytes around plaques | In vitro and in vivo (Tg-SwDI and Tg2576 mice) | [45] |
| MMP-3 | Increased expression upon stimulation with A | In vitro (astrocyte and mixed hippocampal cultures) | [46] |
| Increased expression in microglia after stimulation with A | In vitro (microglial cell line Ra2) | [47] |
| Involved in synaptic plasticity | In vivo (rats) | [48] |
| Significantly upregulated plasma and levels correlate with CSF | Patients (plasma and CSF) | [49] |
| Ability to degrade Aβ | In vitro (APP-CHO cells ) | [50] |
| Increased expression | In vivo (icv injection of Aβ oligomers) | [32] |
| Increased BCSFB permeability | In vivo (icv injection of Aβ oligomers) | [32] |
| MMP-9 | Strong expression in microglia, astrocytes, and endothelial cells in the brain | In vitro (primary cultured dopaminergic neurons) | [51] |
| Biomarker to differentiate AD from dementia | Patients (CSF) | [52] |
| Cognitive impairment | Patient samples | [53] |
| Elevated serum MMP-9 levels | Patient samples | [54] |
| Degrades Aβ fibrils in vitro and Aβ plaques in ex vivo brain slices | In vitro and ex vivo (APP/PS1 and APPsw mice) | [55] |
| Expression detected in neuronal cytoplasm, neurofibrillary tangles, amyloid plaques, and vascular tissue | Patients (postmortem brain tissue) | [56] |
| Detected in astrocytes when treated with soluble and fibrillar A and A | In vitro (primary astrocytes) | [57] |
| MMP-9 can cleave A | In vitro (isolates from patients brains) | [58] |
| Involved in synaptic plasticity | In vivo (rats) | [48] |
| Increased in hippocampus upon intracerebroventricular injection | In vivo (mice) | [59] |
| Regulator of NMDA receptor | In vitro (hippocampal neurons) | [60] |
| BBB disruption, activation of CypA/MMP-9 in pericytes | Patients (CSF) | [61] |
| MMP-12 | Increase in microglia | In vitro (microglial cell line Ra2) | [62] |
| MMP-13 | Increase in microglia | In vitro (microglial cell line Ra2) | [62] |
|
| Parkinson’s disease | MMP-2 | Detected in astrocytes and microglia | Patients | [63] |
| MMP-3 | Activates microglia | In vitro (PC12 cells) | [64] |
| MMP-3 dependent ERK signal pathway activation in microglia | Patients (postmortem brain tissue) | [65] |
| Induces dopaminergic neuron cell death in mesencephalic neuron-glia mixed culture of wild-type | In vitro (neuron-glia mixed culture) | [66] |
| Induce production of NO in microglia | In vitro (primary mesencephalic cultures from NADPH oxidase null or wild-type mice) | [66, 67] |
| MMP-3 secretion by neurons | In vitro (primary cultured dopaminergic neurons of wild-type and MMP-3 knockout) | [51] |
| Proteolysis of α-synuclein | In vitro (human dopaminergic neuroblastoma (SK-N-BE) cell line) | [68] |
| MMP-9 | Increased MMP-9 activity in striatum and substantia nigra after MPTP treatment | In vivo (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD) | [69] |
| MMP-9 was primarily localized in neurons | Patients (postmortem brain tissue) | [63] |
| Increased MMP-9 expression substantia nigra | In vivo (mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD) | [70] |
|
| Amyotrophic lateral sclerosis | MMP-2 | To evaluate ALS disease progression | Patients (serum) | [71] |
| Increased BBB permeability | Patients | [72] |
| MMP-3 | Contributes to motor neuronal cell death | In vivo (G93A SOD1 mice) | [73] |
| MMP-9 | Upregulates neuronal TNF and FasL expression and activation | In vivo (G93A SOD1 mice) | [73] |
| Dysregulated activity with disease progression | In vivo (mutant SOD1 transgenic mice) | [74] |
| Low levels of MMP-9 in CSF | Patients (CSF) | [75] |
| Elevated in skin and CSF | Patients (skin and CSF) | [71] |
| MT-MMP-1/MMP-9 as a marker to distinguish ALS patients from healthy individuals | Patients (serum) | [72] |
| Genetic risk factor for ALS | Patients (peripheral blood leukocytes) | [76] |
|
| Huntington disease | MMP-10 | Cleaves huntingtin | In vitro (striatal cell culture expressing mutant Htt) | [77] |
| MMP-9 | Increased MMP-9 expression | Patients (postmortem brain tissue) | [78] |
| Increased MMP-9 expression | In vivo (3-nitropropionic acid animal model of the disease) | [79] |
| MMP-14 | Knockdown of MMP-14 reduces toxicity | In vitro (striatal cell culture) expressing mutant Htt) | [77] |
| MMP-23 | Knockdown of MMP-23 reduces toxicity | In vitro (striatal cell culture expressing mutant Htt) | [77] |
|
| Multiple sclerosis (MS) | MMP-1 | Expression in macrophages, and weak expression in astrocytes near necrotic lesions | Patients (active lesion sites of postmortem brain samples) | [80] |
| Increased mRNA levels | Patients (monocytes) | [81] |
| MMP-2 | Expression in macrophages and weak expression in astrocytes near necrotic lesions | Patients (active lesion sites of postmortem brain samples) | [80] |
| MMP-3 | Expression in endothelial cells | Patients (active lesion sites of postmortem brain samples) | [80] |
| Increased mRNA levels | Patients (monocytes) | [81] |
| MMP-7 | Secreted by activated macrophages | Patients (active lesion sites of postmortem brain samples) | [82] |
| Increased mRNA levels | Patients (monocytes) | [81] |
| MMP-9 | Secreted by blood vessels | Patients (active lesion sites of postmortem brain samples) | [82] |
| Increased mRNA levels | Patients (monocytes) | [81] |
| Expression in macrophages and weak expression in astrocytes near necrotic lesions | Patients (active lesion sites of postmortem brain samples) | [80] |
| Secreted by T-cells and macrophages, contributes to tissue damage surrounding lesion | Patients (CSF samples from both RRMS and PPMS patients) | [83] |
| Increased levels of MMP-9 in serum along with TIMP-1 and TIMP-2 | Patients (serum) | [84] |
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