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Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-β peptide (1–40).
Open accessAbstract
We reported earlier that the levels of Ca 2+ -dependent metalloproteinases are increased in Alzheimer’s disease (AD) specimens, relative to control specimens. Here we show that these enzymes are forms of the matrix metalloproteinase MMP-9 (EC 3.4.24.35 ) and are expressed in the human hippocampus. Affinity-purified antibodies to MMP-9 labeled pyramidal neurons, but not granular neurons or glial cells. MMP-9 mRNA is expressed in pyramidal neurons, as determined with digoxigenin-labeled MMP-9 riboprobes, and the presence of this mRNA is confirmed with reverse transcriptase PCR. The cellular distribution of MMP-9 is altered in AD because 76% of the total 100 kDa enzyme activity is found in the soluble fraction of control specimens, whereas only 51% is detectable in the same fraction from AD specimens. The accumulated 100 kDa enzyme from AD brain is latent and can be converted to an active form with aminophenylmercuric acetate. MMP-9 also is detected in close proximity to extracellular amyloid plaques. Because a major constituent of plaques is the 4 kDa β-amyloid peptide, synthetic Aβ 1–40 was incubated with activated MMP-9. The enzyme cleaves the peptide at several sites, predominantly at Leu 34 -Met 35 within the membrane-spanning domain. These results establish that neurons have the capacity to synthesize MMP-9, which, on activation, may degrade extracellular substrates such as β-amyloid. Because the latent form of MMP-9 accumulates in AD brain, it is hypothesized that the lack of enzyme activation contributes to the accumulation of insoluble β-amyloid peptides in plaques.
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“Increasing in vitro evidence indicates that some MMPs may play an important role in degrading soluble Ab (sAb), such as secreted MMP-2 and MMP-9 that generate C-terminally truncated Ab fragments and membrane-type MMP-14 that degrades both soluble and fibrillary Ab (29)(30)(31)(32).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [29]
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In the citing paper
“MMP-9 is capable of cleaving Aβ in vitro (Backstrom et al., 1996)”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
In the citing paper
“In parallel, a number of these CNS diseases exhibit dysregulated expression of enzymes necessary for PNN cleavage and reorganization (Backstrom et al., 1996; Lorenzl et al., 2003; Rybakowski et al., 2009; Kim et al., 2009; Zhang et al., 2011; Yamamori et al., 2013; Liu et al., 2014; Rankin-Gee et al., 2015; Lepeta et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
In the citing paper
“plasma levels of MMP-9 are elevated in AD patients (Backstrom et al., 1996; Lorenzl et al., 2003).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
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Items 101–200 of 337
MMP-9 Sheds the β2 Integrin Subunit (CD18) from Macrophages
Vaisar, T., Kassim, S. Y., Gomez, I. G., Green, P. S., Hargarten, S., Gough, P. J., Parks, W. C., Wilson, C. L., Raines, E. W., & Heinecke, J. W. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800449-mcp200 · Cited by 91
“This raises the intriguing possibility that MMP-9 might reduce cerebral amyloid burden by two complementary mechanisms: by impairing production and by increasing the degradation of amyloid- peptide (63, 80, 82, 83).”
Backgroundβ-Amyloid induces the production of active, matrix-degrading proteases in cultured rat astrocytes
Deb, S., Wenjun Zhang, J., & Gottschall, P. E. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02344-8 · Cited by 81
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Matrix metalloproteinases in Alzheimer’s disease and concurrent cerebral microbleeds.
Duits, F. H., Hernandez-Guillamon, M., Montaner, J., Goos, J. D. C., Montañola, A., Wattjes, M. P., Barkhof, F., Scheltens, P., Teunissen, C. E., & van der Flier, W. M. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-143186 · Cited by 92
Aβ accumulation in choroid plexus is associated with mitochondrial-induced apoptosis
Vargas, T., Ugalde, C., Spuch, C., Antequera, D., Morán, M., Martín, M. A., Ferrer, I., Bermejo‐Pareja, F., & Carro, E. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.017 · Cited by 93
Fabbro, S., & Seeds, N. W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05894.x · Cited by 89
Restored degradation of the Alzheimer’s amyloid‐β peptide by targeting amyloid formation
Crouch, P. J., Tew, D. J., Du, T., Nguyen, D., Caragounis, A., Filiz, G., Blake, R. E., Trounce, I. A., Soon, C. P. W., Laughton, K. M., et al. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05870.x · Cited by 88
García-González, L., Pilat, D., Baranger, K., & Rivera, S. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00244 · Cited by 88
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“Several MMPs, including MMP-2, MMP-9 and membranetype 1-MMP (MT1-MMP), a principal activator of MMP-2, may degrade Aβ (Roher et al., 1994; Backstrom et al., 1996; Yin et al., 2006; Liao and Van Nostrand, 2010).”
BackgroundMatrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines
Stawarski, M., Stefaniuk, M., & Włodarczyk, J. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00068 · Cited by 87
“The ability of MMP9 to cleave β-amyloid peptide is particularly interesting because an increase in MMP-9 expression was observed in Alzheimer’s disease patients by several research groups (Backstrom et al., 1996; Yan et al., 2006; Mizoguchi et al., 2011a; Filippov and Dityatev, 2012).”
BackgroundECM in brain aging and dementia
Morawski, M., Filippov, M., Tzinia, A., Tsilibary, E., & Vargova, L. (2014) · Progress in Brain Research · doi:10.1016/b978-0-444-63486-3.00010-4 · Cited by 84
“Increased levels of MMP-9 have been observed in the brain of AD patients (Backstrom et al., 1996; Baig et al., 2008) and in reactive astrocytes surrounding amyloid plaques (Baig et al., 2008; Yan et al., 2006; Yin et al., 2006), suggesting a local tissue response to plaque accumulation.”
Targeting Amyloid‐Degrading Enzymes as Therapeutic Strategies in Neurodegeneration
Turner, A. J., Fisk, L., & Nalivaeva, N. N. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.001 · Cited by 86
Matrix metalloproteinases and cellular motility in development and disease
VanSaun, M. N., & Matrisian, L. M. (2006) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.20061 · Cited by 83
Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer's 5xFAD mice
Fragkouli, A., Tsilibary, E. C., & Tzinia, A. K. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.06.021 · Cited by 90
The role of neutrophils in the dysfunction of central nervous system barriers
Santos-Lima, B., Pietronigro, E. C., Terrabuio, E., Zenaro, E., & Constantin, G. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.965169 · Cited by 82
Demestre, M., Parkin-Smith, G. F., Petzold, A., & Pullen, A. H. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.09.015 · Cited by 82
“which is MMP-9 complexed with its inhibitor TIMP-1 (Backstrom et al., 1996; Moutsiakis et al., 1992), or associated with neutrophil gelatinase associated lipocalin (Yan et al.”
BackgroundWright, J. W., Kramár, E. A., Meighan, S. E., & Harding, J. W. (2002) · Peptides · doi:10.1016/s0196-9781(01)00599-x · Cited by 81
Neural plasticity and the brain renin–angiotensin system
Wright, J. W., Reichert, J. R., Davis, C. J., & Harding, J. W. (2002) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(02)00019-2 · Cited by 80
Sousa, M. M., do Amaral, B., Guimarães, A., & Saraiva, M. J. (2004) · The FASEB Journal · doi:10.1096/fj.04-2022fje · Cited by 80
“It has been previously reported that MMP-9 is able to degrade amyloid β (25).”
BackgroundUllah, R., Park, T. J., Huang, X., & Kim, M. O. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101451 · Cited by 78
“…angiotensin-converting enzyme (Hemming and Selkoe, 2005; Miners et al., 2008a), plasmin (Exley and Korchazhkina, 2001; Miners et al., 2008a), and matrix metalloproteinases (2, 3, and 9) produced by neurons and glial cells (Backstrom et al., 1996; Miners et al., 2008a; Tarasoff-Conway et al., 2015).”
BackgroundPagenstecher, A., Stalder, A. K., Kincaid, C., Volk, B., & Campbell, I. L. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64531-2 · Cited by 78
Crouch, P. J., White, A. R., & Bush, A. I. (2007) · FEBS Journal · doi:10.1111/j.1742-4658.2007.05918.x · Cited by 78
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Aspects of β-Amyloid as a Biomarker for Alzheimer's Disease
Andréasson, U., Portelius, E., Andersson, M. E., Blennow, K., & Zetterberg, H. (2007) · Biomarkers in Medicine · doi:10.2217/17520363.1.1.59 · Cited by 74
Estrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid degradation
Merlo, S., & Sortino, M. A. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.02.005 · Cited by 77
“In vitro analyses have revealed multiple specific cleavage sites for MMPs in the Aβ aminoacidic sequence (Backstrom et al., 1996; Roher et al., 1994), suggesting a main role for these enzymes in Aβ metabolic fate.”
BackgroundJung, S. S., Zhang, W., & Nostrand, W. E. V. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01745.x · Cited by 71
Kostomoiri, M., Fragkouli, A., Sagnou, M., Skaltsounis, L., Pelecanou, M., Tsilibary, E. C., & Tzinia, A. (2012) · Cellular and molecular neurobiology · doi:10.1007/s10571-012-9880-9 · Cited by 68
“Recent evidence indicates that MMP-9 contributes to the clearance of Ab and has a-secretase-like properties (Backstrom et al. 1996; Yan et al. 2006; Talamagas et al. 2007).”
Matrix metalloproteinase-9 is increased and correlates with severity in Guillain-Barre syndrome
Créange, A., Sharshar, T., Planchenault, T., Christov, C., Poron, F., RAPHAEL, J., & Gherardi, R. K. (1999) · Neurology · doi:10.1212/wnl.53.8.1683 · Cited by 68
Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage
Lee, J., Yin, K., Hsin, I., Chen, S., Fryer, J. D., Holtzman, D. M., Hsu, C. Y., & Xu, J. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.11.041 · Cited by 70
Macrophage-Mediated Degradation of β-Amyloid via an Apolipoprotein E Isoform-Dependent Mechanism
Zhao, L., Lin, S., Bales, K. R., Gelfanova, V., Koger, D., DeLong, C. A., Hale, J. E., Liu, F., Hunter, J. M., & Paul, S. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5302-08.2009 · Cited by 70
“…macrophage-dependent A degradation Multiple proteases have been reported to degrade A , and each protease appears to have cleavage sites that generate unique A fragments (Roher et al., 1994; Howell et al., 1995; Backstrom et al., 1996; Eckman et al., 2001; Kurochkin, 2001; Carson and Turner, 2002).”
BackgroundThe Role of Extracellular Matrix in Human Neurodegenerative Diseases
Pintér, P., & Alpár, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911085 · Cited by 68
Frautschy, S. A., Horn, D. L., Sigel, J. J., Harris-White, M. E., Mendoza, J. J., Yang, F., Saido, T. C., & Cole, G. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08311.1998 · Cited by 65
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Neuroinflammation and Alzheimer’s Disease: A Machine Learning Approach to CSF Proteomics
Gaetani, L., Bellomo, G., Parnetti, L., Blennow, K., Zetterberg, H., & Filippo, M. D. (2021) · Cells · doi:10.3390/cells10081930 · Cited by 67
“Of interest, matrix metalloproteinases are able to degrade Aβ in vitro as well as in vivo in animal models of cerebral amyloidosis [39,40].”
BackgroundThe matrix metalloproteinases and CNS plasticity: An overview
Milward, E. A., Fitzsimmons, C., Szklarczyk, A., & Conant, K. E. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.04.010 · Cited by 63
Degradation of Amyloid β Protein by Purified Myelin Basic Protein
Liao, M.-C., Ahmed, M., Smith, S. O., & Nostrand, W. E. V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.050856 · Cited by 64
Twenty years of metallo-neurobiology: where to now?
Bush, A. I., & Curtain, C. C. (2007) · European Biophysics Journal · doi:10.1007/s00249-007-0228-1 · Cited by 62
“Once inside the cell, Cu and Zn, but not Fe, activated phosphoinositol 3-kinase mediated protein kinase pathways, leading to an increase in the secretion of MMPs whose ability to degrade A has been reported by several groups ( Backstrom et al. 1996; Stix et al. 2001).”
BackgroundKaminari, A., Giannakas, N., Tzinia, A. K., & Tsilibary, E. C. (2017) · Scientific Reports · doi:10.1038/s41598-017-00794-5 · Cited by 62
Regulation of matrix metalloproteinase 2 by oligomeric amyloid β protein
Li, W., Poteet, E. C., Xie, L., Liu, R., Wen, Y., & Yang, S.-H. (2011) · Brain Research · doi:10.1016/j.brainres.2011.02.078 · Cited by 61
“In vitro studies have demonstrated that both MMP2 and MMP9 could degrade Aβ (Backstrom et al., 1996; White et al., 2006) (Yin et al., 2006).”
BackgroundNübling, G., Levin, J., Bader, B., Israel, L., Bötzel, K., Lorenzl, S., & Giese, A. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.07.018 · Cited by 59
“MMP-9 has been localized to hippocampal neurons, NFTs, senile plaques and the vascular wall in post mortem AD brain samples (Asahina et al., 2001; Backstrom et al., 1996).”
BackgroundVetrivel, K. S., Zhang, X., Meckler, X., Cheng, H., Lee, S., Gong, P., Radomski, K. L., Chen, Y., Iwata, N., Yin, K., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801037200 · Cited by 59
Mizoguchi, H., Yamada, K., & Nabeshima, T. (2011) · Biochemistry Research International · doi:10.1155/2011/681385 · Cited by 57
“Although MMP-9 cleaves the Aβ peptide at several sites [62, 67], its role in Aβ-induced cognitive dysfunction and neurotoxicity is unclear.”
BackgroundPharmacotherapeutic targets in Alzheimer's disease
Biran, Y., Masters, C. L., Barnham, K. J., Bush, A. I., & Adlard, P. A. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00595.x · Cited by 59
Effect of γ-synuclein overexpression on matrix metalloproteinases in retinoblastoma Y79 cells
Surgucheva, I. G., Sivak, J. M., Fini, M. E., Palazzo, R. E., & Surguchov, A. P. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00664-1 · Cited by 57
Martín‐Aragón, S., Bermejo‐Bescós, P., Benedı́, J., Felici, E., Gil, P., Ribera, J. M., & Villar, Á. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9789-3 · Cited by 56
“As for MMP-9 (92-kDa gelatinase B), high levels have been detected in plasma and cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS) [7, 8] and prominent expression has been seen in reactive astrocytes and macrophages in demyelinating lesions compared to normal brain tissues [9].”
BackgroundNitric oxide‐mediated regulation of ‐amyloid clearance via alterations of MMP‐9/TIMP‐1
Ridnour, L. A., Dhanapal, S., Hoos, M., Wilson, J., Lee, J., Cheng, R. Y. S., Brueggemann, E. E., Hines, H. B., Wilcock, D. M., Vitek, M. P., et al. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12028 · Cited by 54
Talamagas, A. A., Efthimiopoulos, S., Tsilibary, E. C., Figueiredo‐Pereira, M. E., & Tzinia, A. K. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.07.016 · Cited by 53
“In the hippocampus of AD patients, increased immunoreactivity of the inactive form of MMP-9 was observed around the plaques (Backstrom et al., 1992; Backstrom et al., 1996), whereas a very recent report stated that activated astrocytes surrounding amyloid plaques showed enhanced expression of MMP-2…”
BackgroundHan, Y., Yan, C., & Garner, W. L. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.77 · Cited by 53
“Others have found that MMP-9 in the human hippocampus retains its latent form, whereas active MMP-9 is capable of degrading the b-amyloid peptide (Backstrom et al., 1996; Lim et al., 1997).”
BackgroundEndogenous and synthetic MMP inhibitors in CNS physiopathology.
Baranger, K., Rivera, S., Liechti, F. D., Grandgirard, D., Bigas, J., Seco, J., Tarrago, T., Leib, S. L., & Khrestchatisky, M. (2014) · Progress in Brain Research · doi:10.1016/b978-0-444-63486-3.00014-1 · Cited by 52
Iowa Variant of Familial Alzheimer’s Disease
Tomidokoro, Y., Rostagno, A. A., Neubert, T. A., Lu, Y., Rebeck, G. W., Frangione, B., Greenberg, S. M., & Ghiso, J. A. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090636 · Cited by 54
Tundo, G., Ciaccio, C., Sbardella, D., Boraso, M., Viviani, B., Coletta, M., & Marini, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034376 · Cited by 50
Alzheimer disease: modeling an Aβ-centered biological network
Campion, D., Pottier, C. P., Nicolas, G., Guennec, K. L., & Rovelet‐Lecrux, A. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.38 · Cited by 55
Khuth, S.-T., Akaoka, H., Pagenstecher, A., Verlaeten, O., Belin, M., Giraudon, P., & Bernard, A. (2001) · Journal of Virology · doi:10.1128/jvi.75.17.8268-8282.2001 · Cited by 52
“Astrocytes and neurons were the main source of MMP-2 and MMP-9, as reported elsewhere (1, 25, 55), and the increase in MMP protein levels during the inflammatory process may point to an activated state of infected neurons, already shown by the neuronal localization of IL-6 and TNF-a in the hippocampus of CDV-infected…”
BackgroundGray, E., Thomas, T. L., Betmouni, S., Scolding, N., & Love, S. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318183d003 · Cited by 51
Humpel, C. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00047 · Cited by 53
“MMP-9 is a zinc dependent metalloprotease and initially synthesized as the inactive proenzyme pro-MMP-9, which is cleaved into an active form upon release by other proteases.”
BackgroundInfluentialTargeted proteomics in Alzheimer’s disease: focus on amyloid-β
Portelius, E., Zetterberg, H., Gobom, J., Andréasson, U., & Blennow, K. (2008) · Expert Review of Proteomics · doi:10.1586/14789450.5.2.225 · Cited by 52
Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer’s type
Martino Adami, P. V., Orellana, A., García, P., Kleineidam, L., Alarcón-Martín, E., Montrreal, L., Aguilera, N., Espinosa, A., Abdelnour, C., Rosende-Roca, M., et al. (2022) · Brain · doi:10.1093/brain/awac024 · Cited by 46
Mlekusch, R., & Humpel, C. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.09.043 · Cited by 49
“An accumulation of MMPs in AD brains in the proximity of extracellular amyloid plaques has been shown [2] and a reduction of MMPs may contribute to Aβ accumulation and consequently to AD development.”
BackgroundWojtunik‐Kulesza, K. A., Rudkowska, M., Kasprzak‐Drozd, K., Oniszczuk, A., & Borowicz, K. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147366 · Cited by 51
“Other potential proteases that degrade Aβ in vitro are: matrix metalloproteases MMP2 and MMP9 [49], angiotensin-converting enzyme [50], and cathepsin D [51].”
BackgroundMagnoni, S., Baker, A. H., George, S. J., Duncan, W. C., Kerr, L. E., McCulloch, J., & Horsburgh, K. J. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.07.020 · Cited by 49
Pagenstecher, A., Wussler, E. M., Opdenakker, G., Volk, B., & Campbell, I. L. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.6.598 · Cited by 49
Hernández‐Guillamón, M., Mawhirt, S. L., Fossati, S., Blais, S. P., Parés, M., Peñalba, A., Boada, M., Couraud, P., Neubert, T. A., Montaner, J., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.135228 · Cited by 49
Terni, B., & Ferrer, I. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142460 · Cited by 46
Pinto, M., Pickrell, A. M., Fukui, H., & Moraes, C. T. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.04.014 · Cited by 47
“Besides these proteases, MMPs like MMP2 and MMP9 are partially responsible for oligomer degradation (Backstrom et al., 1996; Roher et al., 1994; Yamada et al., 1995).”
BackgroundMinocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy
Yan, P., Zhu, A., Liao, F., Xiao, Q.-L., Kraft, A. W., Gonzales, E., Perez, R., Greenberg, S., Holtzman, D., & Lee, J.-M. (2015) · Stroke · doi:10.1161/strokeaha.115.008582 · Cited by 35
Mairuae, N., Connor, J., & Cheepsunthorn, P. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.06.001 · Cited by 45
The Link Between Matrix Metalloproteinases and Alzheimer’s Disease Pathophysiology
Radošinská, D., & Radošinská, J. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04315-0 · Cited by 50
“After its activation, this proenzyme form was able to cleave Aβ40 peptides at several sites of the amino acid sequence [54].”
P2Y receptors in Alzheimer's disease
Erb, L., Chen, C., Ajit, D., & Weisman, G. A. (2014) · Biology of the Cell · doi:10.1111/boc.201400043 · Cited by 45
“, 2003) and colocalises with Aβ plaques (Backstrom et al., 1996).”
BackgroundInfluentialDonovan, L. E., Dammer, E. B., Duong, D. M., Hanfelt, J., Levey, A. I., Seyfried, N. T., & Lah, J. J. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt186 · Cited by 43
Motyl, J. A., Wencel, P. L., Cieślik, M., Strosznajder, R. P., & Strosznajder, J. B. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0317-1 · Cited by 42
Behl, T., Kaur, I., Frățilă, O., Brata, R. D., & BUNGAU, S. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207443 · Cited by 47
“Synthetic Aβ peptide cleavage is carried out by MMP9, which is latent in the neural tissue of AD patients, which is the reason for amyloid accumulation in AD patients [89].”
BackgroundCiccone, L., Vandooren, J., Nencetti, S., & Orlandini, E. (2021) · Pharmaceuticals · doi:10.3390/ph14020086 · Cited by 46
“The disease- or damage-mediated induction of MMP-9 is found in the endothelial cells of cerebral vasculature [47], astrocytes surrounding amyloid plaques or in injured nerves [18,48,49], areas of astrogliosis [50], meninges and neurons of the injured spinal cord [51], human pyramidal neurons [52], and Schwann cells st…”
BackgroundJäkel, L., Kuiperij, H. B., Gerding, L. P., Custers, E., van den Berg, E., Jolink, W. M. T., Schreuder, F. H. B. M., Küsters, B., Klijn, C. J. M., & Verbeek, M. M. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00972-z · Cited by 44
Ajmo, J. M., Bailey, L. A., Howell, M. D., Cortez, L. K., Pennypacker, K. R., Mehta, H. N., Morgan, D., Gordon, M. N., & Gottschall, P. E. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06647.x · Cited by 41
Hernández‐Guillamon, M., Delgado, P., Ortega, L., Pares, M., Rosell, A., García‐Bonilla, L., Fernández‐Cadenas, I., Borrell‐Pagès, M., Boada, M., & Montaner, J. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22034 · Cited by 39
“In fact, increased expression of MMP-9 and TIMP-1 has been found around Abeta depositions in post-mortem AD brains (Peress et al., 1995; Backstrom et al., 1996; Asahina et al., 2001).”
BackgroundReview: The renin-angiotensin-aldosterone system and Alzheimer's disease?
Kehoe, P. G. (2003) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.3317/jraas.2003.017 · Cited by 41
The role of metals in modulating metalloprotease activity in the AD brain
Filiz, G., Price, K. A., Caragounis, A., Du, T., Crouch, P. J., & White, A. R. (2008) · European Biophysics Journal · doi:10.1007/s00249-007-0244-1 · Cited by 40
“have suggested that MMPs are synthesised in response to A , and if the latent form of MMP is activated it would further degrade the A peptide in vivo and reduce the aggregation of the peptide in the plaques (Backstrom et al. 1996).”
BackgroundInfluentialKinoshita, M., Nasu-Tada, K., Fujishita, K., Sato, K., & Koizumi, S. (2012) · Cellular and molecular neurobiology · doi:10.1007/s10571-012-9869-4 · Cited by 36
Lee, E. O., Kang, J. L., & Chong, Y. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409101200 · Cited by 39
Weeks, B. S., Nomizu, M., Ramchandran, R. S., Yamada, Y., & Kleinman, H. K. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4157 · Cited by 40
Zhang, L., Postina, R., & Wang, Y. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0121-4 · Cited by 40
“Second, increased expression of both RAGE and MMP9 is found in Ab rich tissues [35, 106].”
BackgroundBaig, S., Kehoe, P. G., & Love, S. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00897.x · Cited by 40
GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson’s Disease and Lewy Body Dementia
Maetzler, W., Deleersnijder, W., Hanssens, V., Bernard, A., Brockmann, K., Marquetand, J., Wurster, I., Rattay, T. W., Roncoroni, L., Schaeffer, E., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149349 · Cited by 36
“MMP9 has been found to co-localize with neurofibrillary tangles, senile plaques and the vascular wall in post-mortem Alzheimer brains [18,19].”
BackgroundCombined Effects of ACE and MMP-3 Polymorphisms On Migraine Development
Kara, İ., Ozkok, E., Aydın, M., Orhan, N., Çetinkaya, Y., Gençer, M., Kilic, G., & Tireli, H. (2007) · Cephalalgia · doi:10.1111/j.1468-2982.2006.01269.x · Cited by 39
Mazzitelli, S., Filipello, F., Rasile, M., Lauranzano, E., Cucuzza, C. S., Tamborini, M., Pozzi, D., Barajon, I., Toni Giorgino, A., Natalello, A., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0381-9 · Cited by 38
Kaminari, A., Tsilibary, E. C., & Tzinia, A. K. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180035 · Cited by 39
“…MMP-9 in particular has been reported to degrade in vitro synthetic A (cid:2) 1 – 40 at the (cid:4) -secretase cleavage site between Lys 16-Leu 17 [41] and in contrast to various proteases involved in A (cid:2) PP processing, MMP-9 has been shown to be the onlyA (cid:2)…”
Tuna, G., Yener, G., Oktay, G., İşlekel, H., & Kirkali, F. G. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180752 · Cited by 42
Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses
Wiera, G., & Mozrzymas, J. W. (2021) · Cells · doi:10.3390/cells10082055 · Cited by 36
“Finally, neuronal MMP9 may cleave and degrade β-amyloid peptide in brains of patients suffering from the Alzheimer’s disease [92].”
BackgroundBajor, M., Michaluk, P., Gulyássy, P., Kékesi, K. A., Juhász, G. D., & Kaczmarek, L. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07829.x · Cited by 38
Matrix Metalloproteinase-9 Reduces Islet Amyloid Formation by Degrading Islet Amyloid Polypeptide
Aston‐Mourney, K., Zraika, S., Udayasankar, J., Subramanian, S. L., Green, P. S., Kahn, S. E., & Hull, R. L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.438457 · Cited by 36
Tondo, G., Marchi, F. D., Bonardi, F., Menegon, F., Verrini, G., Aprile, D., Anselmi, M., Mazzini, L., & Comi, C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13113098 · Cited by 45
“Previous experimental studies have shown the ability of MMP9 to degrade A β peptides [204,205], and its regulation may represent a favorable target for stimulating A β clearance [206].”
BackgroundSex differences in Alzheimer’s disease: plasma MMP-9 and markers of disease severity
Tsiknia, A. A., Sundermann, E. E., Reas, E. T., Edland, S. D., Brewer, J. B., Galasko, D. R., Banks, S. J., & Initiative, A. D. N. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01106-4 · Cited by 39
“Several studies have demonstrated that MMP-9 promotes Aβ clearance by degrading aggregate Aβ fibrils [6, 17, 40], and 17β-estradiol treatment was shown to enhance MMP-9 catabolism of Aβ42 [33].”
BackgroundHsieh, M., Ho, H., Chou, D., Pan, S., Liang, Y., Hsieh, T., Lan, J., & Tsai, S. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10530 · Cited by 35
“MMP-9 also plays a role in many other disease states including Alzheimer’s disease [Fujimoto et al., 1996].”
BackgroundMolecular basis of selective amyloid‐β degrading enzymes in Alzheimer's disease
Żukowska, J., Moss, S. J., Subramanian, V., & Acharya, K. R. (2023) · FEBS Journal · doi:10.1111/febs.16939 · Cited by 36
Effects of apoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes
Guo, S., Wang, S., Kim, W. J., Lee, S.-R., Frosch, M. P., Bacskai, B. J., Greenberg, S. M., & Lo, E. H. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.041 · Cited by 34
Serotonin‐induced activation of the network for locomotion in adult spinal rats
Feraboli‐Lohnherr, D., Barthe, J., & Orsal, D. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990101)55:1 · Cited by 106
Lézin, A., Buart, S., Smadja, D., Akaoka, H., Bourdonné, O., Perret‐Liaudet, A., Césaire, R., Belin, M., & Giraudon, P. (2000) · AIDS Research and Human Retroviruses · doi:10.1089/08892220050058380 · Cited by 32
“Association of overexpression of MMP-9 in nervous tissue from patients with neurological disease, 24,45 and a newly evidenced induction of apoptosis by TIMP-3, 46,47 provide an important basis for further investigations addressing the role of TIMP-3 in pathogenesis.”
Zuroff, L. R., Torbati, T., Hart, N. J., Fuchs, D.-T. S., Sheyn, J., Rentsendorj, A., Koronyo, Y., Hayden, E. Y., Teplow, D. B., Black, K. L., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01449 · Cited by 29
Fabbro, S., Schaller, K., & Seeds, N. W. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07359.x · Cited by 31
Metadata
- Authors
- Backstrom, J. R., Lim, G. P., Cullen, M. J., & Tökés, Z. A.
- Affiliations
- University of Southern California (US)
- ORCID
- Cullen, Michael J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-12-15
- Volume
- 16
- Issue
- 24
- Pages
- 7910-7919
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4296941341
- Cited by
- 331
- References
- 46
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 16 · 2020: 21 · 2019: 5 · 2018: 13 · 2017: 15 · 2016: 11 · 2015: 18 · 2014: 18 · 2013: 8 · 2012: 12
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Funders
- National Institute on Aging (R01-AG09681)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- MMP-9, Alzheimer's disease, Aβ40, hippocampal pyramidal neurons, MMP-9 mRNA expression, extracellular matrix metalloproteinases, transmembrane domain
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