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Matrix Metalloproteinase-9 Degrades Amyloid-β Fibrils in Vitro and Compact Plaques in Situ
Open accessAbstract
The pathological hallmark of Alzheimer disease is the senile plaque principally composed of tightly aggregated amyloid-beta fibrils (fAbeta), which are thought to be resistant to degradation and clearance. In this study, we explored whether proteases capable of degrading soluble Abeta (sAbeta) could degrade fAbeta as well. We demonstrate that matrix metalloproteinase-9 (MMP-9) can degrade fAbeta and that this ability is not shared by other sAbeta-degrading enzymes examined, including endothelin-converting enzyme, insulin-degrading enzyme, and neprilysin. fAbeta was decreased in samples incubated with MMP-9 compared with other proteases, assessed using thioflavin-T. Furthermore, fAbeta breakdown with MMP-9 but not with other proteases was demonstrated by transmission electron microscopy. Proteolytic digests of purified fAbeta were analyzed with matrix-assisted laser desorption ionization time-of-flight mass spectrometry to identify sites of Abeta that are cleaved during its degradation. Only MMP-9 digests contained fragments (Abeta(1-20) and Abeta(1-30)) from fAbeta(1-42) substrate; the corresponding cleavage sites are thought to be important for beta-pleated sheet formation. To determine whether MMP-9 can degrade plaques formed in vivo, fresh brain slices from aged APP/PS1 mice were incubated with proteases. MMP-9 digestion resulted in a decrease in thioflavin-S (ThS) staining. Consistent with a role for endogenous MMP-9 in this process in vivo, MMP-9 immunoreactivity was detected in astrocytes surrounding amyloid plaques in the brains of aged APP/PS1 and APPsw mice, and increased MMP activity was selectively observed in compact ThS-positive plaques. These findings suggest that MMP-9 can degrade fAbeta and may contribute to ongoing clearance of plaques from amyloid-laden brains.
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“and that MMP-9 is capable of degrading amyloid fibrils in vitro and amyloid plaques in situ (61).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [61]
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“We have previously found that the expression of MMP-9 is up-regulated in reactive astrocytes surrounding plaques (61, 62)”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [61]
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“Enhanced expression of MMP-2 and MMP-9 has been found in astrocytes surrounding amyloid plaques and in the neurons and glia of the hippocampus after intracerebroventricular Ab injection (25)(26)(27)(28).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [26]
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Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautschy, S. A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m404751200 · Cited by 2,336
Common core structure of amyloid fibrils by synchrotron X-ray diffraction 1 1Edited by F. E. Cohen
Sunde, M., Serpell, L. C., Bartlam, M. G., Fraser, P. E., Pepys, M. B., & Blake, C. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1348 · Cited by 1,735
Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E. A., Frosch, M. P., Eckman, C. B., Tanzi, R. E., Selkoe, D. J., & Guénette, S. Y. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0230450100 · Cited by 1,526
In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis
Stine, W. B., Dahlgren, K. N., Krafft, G. A., & LaDu, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210207200 · Cited by 1,015
Metabolic Regulation of Brain Aβ by Neprilysin
Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N. P., Gerard, C. J., Hama, E., Lee, H.-J., & Saido, T. C. (2001) · Science · doi:10.1126/science.1059946 · Cited by 982
Alzheimer’s amyloid fibrils: structure and assembly
Serpell, L. C. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00029-6 · Cited by 973
Biochemistry and Molecular Biology of Gelatinase B or Matrix Metalloproteinase-9 (MMP-9)
den Steen, P. E. V., Dubois, B., Nelissen, I., Rudd, P., Dwek, R., & Opdenakker, G. (2002) · Critical reviews in biochemistry and molecular biology · doi:10.1080/10409230290771546 · Cited by 948
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909
Flagged first, then by citations
5 of the 58 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
- Nagase, 1999, J. Biol. Chem., 274, 21491, 10.1074/jbc.274.31.21491 · DOI
- Anthony, 1997, Neuropathol. Appl. Neurobiol., 23, 406, 10.1111/j.1365-2990.1997.tb01315.x · DOI
- Asahina, 2001, Clin. Neuropathol., 20, 60
- Nilsson, 2004, Methods (Amst.), 34, 151
- McGeer, 2001, Mol. Interv., 1, 22
- Iannone, 2003, J. Rheumatol., 30, 2294
- Dubois, 1999, Acta Neurol. Belg., 99, 53
Cited by
Sorted by citations
Items 101–200 of 334
Trikha, S., & Jeremic, A. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.240762 · Cited by 75
García-Alloza, M., Prada, C. M., Lattarulo, C. R., Fine, S., Borrelli, L. A., Betensky, R. A., Greenberg, S. M., Frosch, M. P., & Bacskai, B. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06096.x · Cited by 65
“It has been reported that MMP-9 can degrade Ab in APP/PS1dE9 mice (Yan et al. 2006) and may contribute to clearance of Ab.”
Cook, J. J., Wildsmith, K. R., Gilberto, D. B., Holahan, M. A., Kinney, G. G., Mathers, P. D., Michener, M. S., Price, E. A., Shearman, M. S., Simon, A. J., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1381-10.2010 · Cited by 72
“Potential candidates known to cleave at the A 1-17 site include endothelin converting enzyme, insulin-degrading enzyme, and matrix metalloproteinase-9 (Yan et al., 2006).”
BackgroundSelf-citationPy, N. A., Bonnet, A. E., Bernard, A., Marchalant, Y., Charrat, E., Checler, F., Khrestchatisky, M., Baranger, K., & Rivera, S. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00247 · Cited by 76
“…MMP-9 and MT1MMP immunostaining were particularly prominent in amyloid plaques, it is possible that they contribute to gelatinolysis in a significant manner, which would be consistent with the singular ability of both MMPs to degrade fibrillar Aβ (Yan et al., 2006; Liao and Van Nostrand, 2010).”
ResultZipfel, G. J., Han, H., Ford, A. L., & Lee, J. (2008) · Stroke · doi:10.1161/strokeaha.108.533174 · Cited by 70
Self-citationThe Biphasic Role of Microglia in Alzheimer's Disease
Mizuno, T. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/737846 · Cited by 73
Mizoguchi, H., Yamada, K., & Nabeshima, T. (2011) · Biochemistry Research International · doi:10.1155/2011/681385 · Cited by 57
“Because MMP-9 has been reported to cleave insoluble Aβ in vitro [67], it was thought that MMP inhibitors may potentiate Aβ-induced cognitive dysfunction and neurotoxicity.”
BackgroundMacrophage-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
“…enzymes, but especially MMP-9, which has in contrast to neprilysin and insulindegrading enzyme, recently been shown to degrade fibrillar A 42 (Yan et al., 2006) and is known to be secreted from various cells including macrophages, astrocytes, and microglia (Gottschall et al., 1995; Muir et…”
BackgroundInfluentialKostomoiri, 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).”
Modulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection
Brown, M. R., Radford, S. E., & Hewitt, E. W. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.609073 · Cited by 67
“MMP-9 was also found to degrade compact Aβ amyloid plaques in brain sections from AD model (APP/PS1) mice (Yan et al., 2006).”
BackgroundRecent Advances in the Study of Bipolar/Rod-Shaped Microglia and their Roles in Neurodegeneration
Au, N. P. B., & Ma, C. H. E. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00128 · Cited by 87
“Microglia secrete proteolytic enzymes such as neprilysin, matrix metalloproteinase 9 (MMP-9), plasminogen and insulindegrading enzyme (IDE), which are capable of degrading β-amyloid peptides (Leissring et al., 2003; Yan et al., 2006).”
BackgroundKim, J. A., Ha, S., Shin, K. Y., Kim, S., Lee, K. J., Chong, Y. H., Chang, K.-A., & Suh, Y.-H. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.138 · Cited by 70
Why Did Tarenflurbil Fail in Alzheimer's Disease?
Imbimbo, B. P. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1092 · Cited by 75
“loproteinase 9 [25], and plasminogen [26], further suggesting a neuroprotective role for these cells in AD.”
Lim, N. K.-H., Villemagne, V. L., Soon, C. P. W., Laughton, K. M., Rowe, C. C., McLean, C., Masters, C. L., Evin, G. M., & Li, Q. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101974 · Cited by 67
“MMP-2 and MMP-9 are both able to degrade A [26, 28] and their expression is increased in AD hippocampal tissue [25] and in astrocytes near the amyloid plaques in AD transgenic mice [27].”
Tryptophan metabolites modify brain Aβ peptide degradation: A role in Alzheimer’s disease?
Maître, M., Klein, C., Patte‐Mensah, C., & Mensah‐Nyagan, A. G. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101800 · Cited by 69
“Both MMP-2 and MMP-9 are also over-expressed in astrocytes surrounding senile plaques in AD transgenic mice brain (APP/PS1 and APPswe) (Yan et al., 2006; Yin et al., 2006).”
BackgroundBaranger, K., Giannoni, P., Girard, S. D., Girot, S., Gaven, F., Stephan, D., Migliorati, M., Khrestchatisky, M., Bockaert, J., Marchetti, E., et al. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.08.031 · Cited by 71
“As previously demonstrated, 5-HT4R activation induces the production of MMP-9 (Hashimoto et al., 2012), a metalloproteinase that can degrade soluble and fibrillar forms of Aβ (Py et al., 2014; Yan et al., 2006).”
BackgroundSon, S. M., Kang, S., Choi, H., & Mook‐Jung, I. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0054-3 · Cited by 64
“These include proteolytic degradation of extracellular Aβ by cell surface-localized and/or secreted proteases such as neprilysin (NEP), matrix metalloproteinase-9 (MMP-9), and insulin-degrading enzyme (IDE) [7–9].”
Glial Draper Rescues Aβ Toxicity in aDrosophilaModel of Alzheimer's Disease
Ray, A., Speese, S. D., & Logan, M. A. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0862-17.2017 · Cited by 79
“Mmp expression is induced upon exposure to soluble and fibrillar A in microglia and astrocytes (Deb et al., 2003; Yan et al., 2006; Ito et al., 2007), and Mmp overexpression in AD model mice attenuates A oligomer formation and rescues cognitive defects (Fragkouli et al.”
BackgroundMetabolic Regulation of Glia and Their Neuroinflammatory Role in Alzheimer's Disease
Kumari, P., Sood, A., & Fernandes, V. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01147-7 · Cited by 68
Mroczko, B., Groblewska, M., & Barcikowska, M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130647 · Cited by 61
“This ability was not shared by other enzymes that degrade sA , including endothelinconverting enzyme, insulin-degrading enzyme, and neprilysin [19] (Table 2).”
InfluentialRegulation 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
“Consistently, significant increases of Aβ have been found in the brains of MMP2 or MMP9 knockout mice (Yan et al., 2006).”
BackgroundZheng, Z., Sabirzhanov, B. E., & Keifer, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.150821 · Cited by 68
Novel targets in Alzheimer’s disease: A special focus on microglia
Balducci, C., & Forloni, G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.01.017 · Cited by 62
Kaminari, A., Giannakas, N., Tzinia, A. K., & Tsilibary, E. C. (2017) · Scientific Reports · doi:10.1038/s41598-017-00794-5 · Cited by 62
Takamatsu, K., Ikeda, T., Haruta, M., Matsumura, K., Ogi, Y., Nakagata, N., Uchino, M., Ando, Y., Nishimura, Y., & Senju, S. (2014) · Stem Cell Research · doi:10.1016/j.scr.2014.10.001 · Cited by 69
Nübling, 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
“As described for MMP-3, synthesis of MMP-9 can also be induced by Aβ, and the enzyme appears to play a role in senile plaque homoeostasis, since it is able to degrade Aβ aggregates in vitro and in situ (Backstrom et al., 1996; Deb et al., 2003; Nagele et al., 2004; Yan et al., 2006).”
BackgroundCzuba, E., Steliga, A., Lietzau, G., & Kowiański, P. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0015-3 · Cited by 62
“Additionally, the MMP-9 degrades Aβ fibrils and in this way contributes to the removal of amyloid plaques from the human brain (Yan et al. 2006).”
Backgroundγ‐Secretase component presenilin is important for microglia β‐amyloid clearance
Farfara, D., Trudler, D., Segev‐Amzaleg, N., Galron, R., Stein, R., & Frenkel, D. (2010) · Annals of Neurology · doi:10.1002/ana.22191 · Cited by 57
“We focused on 3 different gene expression profiles linked to microglia function toward Ab: activation markers (CD11b, iNOS, TNFa, IL-6, SRA, and Toll-like receptor 2 [TLR-2])(10); migration marker (CCR2)(12); and expression of enzymes that degrade Ab such as insulin-degrading enzyme (IDE)(27) and matrix metalloprotein…”
BackgroundSkaat, H., Sorci, M., Belfort, G., & Margel, S. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32232 · Cited by 64
Khandelwal, M., Manglani, K., Upadhyay, P., Azad, M., & Gupta, S. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105876 · Cited by 56
“The immunohistochemistry of the brain sections using Aβ42 antibody and staining with ThS was performed and analyzed for the dense core of amyloid plaque in the brain (Yan et al., 2006).”
MethodHerring, A., Lewejohann, L., Panzer, A.-L., Donath, A., Kröll, O., Sachser, N., Paulus, W., & Keyvani, K. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.03.007 · Cited by 63
Carty, N. C., Nash, K., Lee, D. C., Mercer, M., Gottschall, P. E., Meyers, C., Muzyczka, N., Gordon, M. N., & Morgan, D. (2008) · Molecular Therapy · doi:10.1038/mt.2008.148 · Cited by 55
Nitric 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
“…impact of NOS2/NO on MMP activity and Ab degradation in our AD models, we developed an antibody recognizing Ab1-16, which is a stable and non-toxic digestion product of Ab1-42 in the presence of active gelatinase enzymes MMP-2 and MMP-9 (Figure S1 and Table S1) (Roher et al. 1994; Yan et al. 2006).”
BackgroundMethodInfluentialSelf-citationBubak, A. N., Como, C. N., Coughlan, C. M., Johnson, N. R., Hassell, J. E., Mescher, T., Niemeyer, C. S., Mahalingam, R., Cohrs, R., Boyd, T. D., et al. (2019) · Journal of Infectious Diseases · doi:10.1093/infdis/jiz560 · Cited by 54
Effect of Proinflammatory Gene Polymorphisms on the Risk of Alzheimer's Disease
Flex, A., Giovannini, S., Biscetti, F., Liperoti, R., Spalletta, G., Straface, G., Landi, F., Angelini, F., Caltagirone, C., Ghirlanda, G., et al. (2013) · Neurodegenerative Diseases · doi:10.1159/000353395 · Cited by 57
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
Wilcock, D. M., Morgan, D., Gordon, M. N., Taylor, T. L., Ridnour, L. A., Wink, D. A., & Colton, C. A. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-115 · Cited by 58
“In vitro MMP2 and MMP9 have both been shown to proteolyze Ab [44,45].”
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
Self-citationLan, Z., Chen, L., Fu, Q., Ji, W., Wang, S.-Y., Liang, Z., Qu, R., Kong, L., & Ma, S.-P. (2013) · Brain Research · doi:10.1016/j.brainres.2012.12.040 · Cited by 51
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
“Furthermore, active matrix metalloproteinase-9 (MMP-9) has been reported to degrade in vitro synthetic Aβ(1–40) at the α-secretase cleavage site between Lys 16-Leu 17 and amyloid beta fibrils (Backstrom et al., 1996; Yan et al., 2006).”
BackgroundTundo, 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
“Somatostatin effect on MMP-9 activity In addition to their ability to phagocyte b-amyloid, microglia can also clear Ab by degradation through the production of Abdegrading enzymes, such as IDE, neprilysin and MMP-9 [29,33,39].”
BackgroundHumpel, C. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00047 · Cited by 53
“Studies examining different fragments of Aβ report on the importance of 2 critical regions for aggregation at positions 17–21 and 30–35 (see Yan et al., 2006).”
BackgroundMethodResultInfluentialFK506 Reduces Amyloid Plaque Burden and Induces MMP-9 in AβPP/PS1 Double Transgenic Mice
Hong, H., Hwang, J.-Y., Son, S., Kim, Y., Moon, M., & Mook-Jung, I. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100261 · Cited by 49
“In particular, it has been demonstrated that MMP-9 can degrade fibrillar forms of A β [32], a finding that is entirely consistent with a reduction in insoluble A β in our FK506 treated mice.”
Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes
Miners, J. S., Palmer, J. C., Tayler, H. M., Palmer, L. E., Ashby, E. L., Kehoe, P. G., & Love, S. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00238 · Cited by 43
“Other groups reported that other candidate Aβ-degrading proteases, including MMP-2 -3 and -9 (Yan et al., 2006; Bruno et al., 2009), cathepsin D (Gan et al., 2004; Mueller-Steiner et al., 2006; Sundelof et al., 2010) and APEH (Yamin et al., 2009), were also increased in human post-mortem brain…”
BackgroundDong, Y., Dekens, D. W., Deyn, P. P. D., Naudé, P. J. W., & Eisel, U. L. M. (2015) · Antibodies · doi:10.3390/antib4040369 · Cited by 50
Ullah, R., & Lee, E. J. (2023) · Experimental Neurobiology · doi:10.5607/en23014 · Cited by 51
“Multiple MMPs including MMP2 and MMP9 [115, 116], have been reported in the degradation of both monomeric and fibrillar forms of amyloid-β [115, 117].”
BackgroundMroczko, B., Groblewska, M., Zboch, M., Kulczyńska, A., Koper, O. M., Szmitkowski, M., Kornhuber, J., & Lewczuk, P. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-131634 · Cited by 57
“briefly summarized in the Table 2 [11, 13, 15, 23–29].”
The use of mass spectrometry to study amyloid‐β peptides
Grasso, G. (2010) · Mass Spectrometry Reviews · doi:10.1002/mas.20281 · Cited by 51
“Only few metalloproteases can degrade Ab fibrils as well as the monomers (Yan et al., 2006), and IDE is not among them.”
BackgroundMethodThe 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
“This idea is supported by an observation of MMP-9 ability to digest Aβ fibrils in vitro and compact plaques in vivo [31].”
Abe, K., Chiba, Y., Hattori, S., Yoshimi, A., Asami, T., Katsuse, O., Suda, A., & Hishimoto, A. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116989 · Cited by 41
Ma, D., Doi, Y., Jin, S., Li, E., Sonobe, Y., Takeuchi, H., Mizuno, T., & Suzumura, A. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.08.071 · Cited by 47
Mairuae, N., Connor, J., & Cheepsunthorn, P. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.06.001 · Cited by 45
Choi, M.-S., Kim, Y. E., Lee, W., Choi, J., Park, G. H., Kim, S. D., Jeon, S., Go, H. S., Shin, S.-M., Kim, W.-K., et al. (2008) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2008.02.031 · Cited by 45
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
“Similar outcomes were reported in vivo in neuronal tissue in APP/PS1 mice [90].”
ResultImai, K., Kotani, T., Tsuda, H., Mano, Y., Nakano, T., Ushida, T., Li, H., Miki, R., Sumigama, S., Iwase, A., et al. (2016) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2015.12.015 · Cited by 44
Zhang, L., Postina, R., & Wang, Y. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0121-4 · Cited by 40
“MMP9 can degrade both soluble Ab and tightly aggregated Ab fibrils, while other Ab degrading enzymes including endothelin-converting enzyme, insulin-degrading enzyme and neprilysin can only degrade soluble Ab, implying the significant contribution of MMP9 to clearance of plaques in amyloid-laden brains [107].”
BackgroundEmerging roles of N- and C-terminally truncated Aβ species in Alzheimer’s disease
Wirths, O., & Zampar, S. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1702972 · Cited by 44
“In addition to C-terminal truncated Aβ peptides that can be directly generated by enzymatic cleavage from β-CTFs as a precursor, further Aβ1-x fragments have been identified that are most likely generated upon degradation of fulllength Aβ, such Aβ1-20, Aβ1-30 or Aβ1-34 [160].”
InfluentialPotential Enzymatic Targets in Alzheimer’s: A Comprehensive Review
Alam, J., & Sharma, L. K. (2018) · Current Drug Targets · doi:10.2174/1389450119666180820104723 · Cited by 56
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
Passos, G. F., Figueiredo, C. P., Prediger, R. D., Silva, K. A. B. S., Siqueira, J. M., Duarte, F. S., Leal, P. C., Medeiros, R., & Calixto, J. Β. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.12.003 · Cited by 55
“Multiple lines of evidence suggest that chemo-attractants are key components in the progression of chronic inflammatory diseases, including AD (Giri et al., 2005; Yan et al., 2006; El Khoury et al., 2007).”
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
Luo, Y.-P., Yang, W., Li, N., Yang, X., Zhu, B.-L., Wang, C., Hou, W.-S., Wang, X., Wen, H., & Tian, X.-L. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00134 · Cited by 42
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
“In 3-month-old APPsw mice, before the accumulation of plaques, MMP-9 immunoreactivity was reported to be absent (Lee et al. 2003), however levels were elevated in astrocytes surrounding plaques in older, plaquebearing mice (Lee et al. 2005; Yan et al. 2006).”
InfluentialThe role of glia in protein aggregation
Li, Q., & Haney, M. S. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105015 · Cited by 54
“Many MMPs are secreted, and MMP2 and MMP9 are two well studied members, which can digest both monomeric and fibrillar Aβ (Ries and Sastre, 2016; Yan et al., 2006).”
BackgroundP2Y 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
“, 2006), and compact plaques in situ (Yan et al., 2006).”
BackgroundHernández‐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
“Another increasingly relevant family of proteases that has been shown to degrade Abeta in vitro is the matrix metalloproteinases (MMPs), specifically two gelatinases, MMP-2 (Roher et al., 1994) and MMP-9 (Backstrom et al., 1996; Yan et al., 2006).”
BackgroundInfluentialTondo, 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].”
BackgroundZraika, S., Aston‐Mourney, K., Marek, P., Hull, R. L., Green, P. S., Udayasankar, J., Subramanian, S. L., Raleigh, D. P., & Kahn, S. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.082032 · Cited by 41
Multiple inflammatory profiles of microglia and altered neuroimages in APP/PS1 transgenic AD mice
Liu, L., Liu, Y., Li, N., Huang, R., Zheng, X., Huang, L., Hou, S.-X., & Yuan, Q. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.01.003 · Cited by 71
de la Vega, M. P., Giedraitis, V., Michno, W., Kilander, L., Güner, G., Zielinski, M., Löwenmark, M., Brundin, R., Danfors, T., Söderberg, L., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc6184 · Cited by 40
Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer’s Disease
Loeffler, D. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201182 · Cited by 71
Domínguez-Prieto, M., Velasco, A. L., Tabernero, A., & Medina, J. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180332 · Cited by 43
Kurapati, K. R. V., Samikkannu, T., Atluri, V. S. R., Kaftanovskaya, E. M., Yndart, A., & Nair, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112818 · Cited by 37
Targeting CaN/NFAT in Alzheimer’s brain degeneration
Mackiewicz, J., Lisek, M., & Boczek, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1281882 · Cited by 41
Ciccone, 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…”
BackgroundInfluentialGDF15/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
“Neurodegenerative Marker Analysis Neurodegenerative markers (CSF Abeta1-42, total Tau and phospho-Tau) were determined using Innotest1 ELISA kits #80324, #80323, or #80317, respectively (Fujirebio Germany GmbH, Hannover, Germany).”
BackgroundInfluentialMetallostasis and amyloid β-degrading enzymes
Grasso, G., Giuffrida, M. L., & Rizzarelli, E. (2012) · Metallomics · doi:10.1039/c2mt20105d · Cited by 41
Kinoshita, 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, S. Y., Kim, H. J., Lee, W. J., Joo, S. H., Jeon, S.-J., Kim, J., Kim, H. S., Han, S., Lee, J., Park, S. H., et al. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9737-2 · Cited by 34
Self-citationMotyl, 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
Minocycline 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
Self-citationMolecular 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
“[122] have shown A b 1 – 42 degradation in many locations by NEP at residues Glu3-Phe4 and Val18-Phe19.”
InfluentialNeuroinflammation in Alzheimer's disease and beneficial action of luteolin
Delgado, A., Cholevas, C., & Theoharides, T. C. (2021) · BioFactors · doi:10.1002/biof.1714 · Cited by 48
“61–64 Microglia are believed to serve an initial, neuroprotective role through the phagocytic clearance of Aβ and the release of Aβ degrading enzymes.(65,66) Yet, the cell's prolonged activity eventually renders them capable of contributing to an environment of neurotoxicity through sustained release of proinflammator…”
BackgroundMazzitelli, 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
“MMP9 in particular, which generates different C-terminal truncated Aβ fragments, including 1–16, 1–20, 1–23, 1–30, 1–33 and 1–34 [19, 23], is thought to play relevant roles in different pathological contexts, as suggested by the observation that its expression can be stimulated by diverse insults, including Aβ itself…”
Gough, M., Parr-Sturgess, C. A., & Parkin, E. T. (2010) · Biochemistry Research International · doi:10.1155/2011/721463 · Cited by 37
“35) have all been shown to possess Aβdegrading activity in vitro; however, unlike ECE-1, NEP, and IDE, MMP-9 is capable of cleaving aggregated Aβ fibrils [137].”
BackgroundTakata, K., Ginhoux, F., & Shimohama, S. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114754 · Cited by 40
Stefano, M. E. D., & Herrero, M. T. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.08.002 · Cited by 42
“Limitation in the glial scar formation by MMP-2 has also been proposed by studies on MMP-2 deficient mice, in which structural and functional recovery of the spinal cord after injury is impaired because of increased glial scarring (Hsu et al., 2006).”
ElAli, A., Bordeleau, M., Thériault, P., Filali, M., Lampron, A., & Rivest, S. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.279 · Cited by 32
Pathogenic prions deviate PrPC signaling in neuronal cells and impair A-beta clearance
Pradines, E., Hernandez-Rapp, J., Villa-Díaz, A., Dakowski, C., Ardila-Osorio, H., Haïk, S., Schneider, B., Launay, J., Kellermann, O., Torres, J., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2012.195 · Cited by 33
Kim, M.-J., Chae, S. S., Koh, Y., Lee, S. K., & Jo, S. (2010) · The FASEB Journal · doi:10.1096/fj.09-148825 · Cited by 33
“(22, 24), which could be advantageous for A clear-”
BackgroundZuroff, 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
Jäkel, 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
Dysregulated Metabolism of the Amyloid‐β Protein and Therapeutic Approaches in Alzheimer Disease
Kikuchi, K., Kidana, K., Tatebe, T., & Tomita, T. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26129 · Cited by 34
“Moreover, MMP-2 and -9 can degrade monomeric and fibrillary Ab [Yan et al., 2006].”
BackgroundAmniotic Mesenchymal Stem Cells Decrease Aβ Deposition and Improve Memory in APP/PS1 Transgenic Mice
Zheng, X., Wan, Q.-Q., Zheng, C.-Y., Zhou, H., Dong, X., Deng, Q., Yao, H., Fu, Q., Gao, M., Yan, Z., et al. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2226-8 · Cited by 37
“Neprilysin (NEP), insulin-degrading enzyme (IDE), and matrix metallo-proteinase 9 (MMP-9) are important Aβ-degrading enzymes [32, 33].”
BackgroundHo, M., Hoke, D., Yee, J.-C., Li, Q.-X., Culvenor, J., Masters, C., White, A., & Evin, G. (2010) · International Journal of Alzheimer's Disease · doi:10.4061/2011/950932 · Cited by 32
“Data suggest that Ca2+ and Mg2+ stabilize γ-secretase and enhance its activity.”
Beta-amyloidolysis and glutathione in Alzheimer's disease
Lasierra-Cirujeda, J., Coronel, Gimeno, & Aza (2013) · Journal of Blood Medicine · doi:10.2147/jbm.s35496 · Cited by 35
Dafnis, I., Tzinia, A. K., Tsilibary, E. C., Zannis, V. I., & Chroni, A. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.03.013 · Cited by 32
“MMP9 has been reported to cleave Aβ fibrils in vitro as well as compact plaques in situ, thus contributing to the ongoing clearance of plaques from amyloid-laden brains (Yan et al., 2006).”
BackgroundOu-Yang, M.-H., & Van Nostrand, W. E. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-134 · Cited by 30
“In regards to Aβ-degrading enzymes, MMP-2 and MMP-9 are distinctive in that both can degrade soluble Aβ peptides and fibrillar plaque Aβ [74-78].”
BackgroundKaminari, A., Tsilibary, E. C., & Tzinia, A. K. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180035 · Cited by 39
Microglia‐targeted stem cell therapies for Alzheimer disease: A preclinical data review
Shen, Z., Li, X., Bao, X., & Wang, R. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24066 · Cited by 32
“7.3 | Ab-degrading enzymes Apart from phagocytosis of Ab, microglia also degrade Ab by secreting proteolytic enzymes, such as insulin-degrading enzyme (IDE), neprilysin (NEP), matrix metalloproteinase 9 (MMP-9), and plasminogen (Leissring et al., 2003; Yan et al., 2006).”
BackgroundInfluential
Metadata
- Authors
- Yan, P., Hu, X., Song, H., Yin, K., Bateman, R. J., Cirrito, J. R., Xiao, Q., Hsu, F. F., Turk, J. W., Xu, J., Hsu, C. Y., Holtzman, D. M., & Lee, J.-M.
- Affiliations
- Washington University in St. Louis (US)
- Taipei Medical University (TW)
- Corresponding author
- Lee, Jin-Moo
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 281
- Issue
- 34
- Pages
- 24566-24574
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2097292535
- Cited by
- 380
- References
- 58
- Citations by year
- 2026: 16 · 2025: 9 · 2024: 16 · 2023: 21 · 2022: 13 · 2021: 21 · 2020: 30 · 2019: 13 · 2018: 19 · 2017: 28 · 2016: 11 · 2015: 26 · 2014: 28 · 2013: 17 · 2012: 26
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p60dk020579-35, 5p41rr000954-34, DK20579, P60-DK-20579, DK56341, P41 RR00954, AG13956)
- U.S. Public Health Service (P60-DK-20579, P41‐RR‐00954, P30‐DK‐56341)
- National Institute on Aging (L30 AG024455, K08AG027091, AG13956)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK20579, P30-DK56341, P30DK056341)
- National Institute of Neurological Disorders and Stroke (NS048283, R01NS048283)
- National Center for Research Resources (P41 RR-00954)
- 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, amyloid-beta fibrils, amyloid plaques, Alzheimer's disease, amyloid beta degradation, proteolytic cleavage sites, APP/PS1 mice, astrocytes, plaque clearance, thioflavin T staining
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Humans, Hydrolysis, Immunohistochemistry, Mice, Transgenic, Mass Spectrometry, Substrate Specificity, Amyloid beta-Peptides, Matrix Metalloproteinase 9, Mice, Plaque, Amyloid
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