The DOI matches its Crossref record; 53 of the 58 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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 201–300 of 334
Amelioration of amyloid-β-induced deficits by DcR3 in an Alzheimer’s disease model
Liu, Y., Chen, W.-T., Lin, Y.-Y., Lu, P.-H., Hsieh, S.-L. E., & Cheng, I. H.-J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0173-0 · Cited by 29
“It is interesting to note that DcR3 did not alter the expression of MMP9, which contributes to plaque clearance in the brain [33], suggesting MMP9-dependent proteolytic degradation of Aβ was not influenced by DcR3 (Additional file 11: Figure S9b).”
Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases
Gargiulo, S., Gamba, P., Poli, G., & Leonarduzzi, G. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660701 · Cited by 34
“Tetracycline derivatives that penetrate the BBB, such as doxycycline and minocycline, downregulate the MMP-3 expression induced by cell stress, cytokines and other stimuli, with subsequent attenuation of neuroinflammation and apoptosis of dopaminergic neurons, both in vitro and in vivo [407-411].”
BackgroundInfluentialMalgieri, G., & Grasso, G. (2013) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2013.10.008 · Cited by 33
Cernescu, M., Stark, T., Kalden, E., Kurz, C., Leuner, K., Deller, T., Göbel, M., Eckert, G. P., & Brutschy, B. (2012) · Analytical Chemistry · doi:10.1021/ac300258m · Cited by 30
Imaging proteomics for diagnosis, monitoring and prediction of Alzheimer's disease
Nazeri, A., Ganjgahi, H., Roostaei, T., Nichols, T. E., & Zarei, M. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.08.041 · Cited by 33
“Moreover, it has been shown that MMP-9 and SOD-1 have anti-A β amyloid properties (Murakami et al., 2011; Yan et al., 2006).”
Sex 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
“Prior studies in animals have shown that in the brain, MMP-9 is directly involved in the degradation and clearance of Aβ, suggesting a more protective rather than destructive role of MMP-9 in AD [6, 17, 18], while others have demonstrated that MMP-9 increases lipoprotein receptor shedding in endothelial cells, leading…”
BackgroundPlasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs
Lee, D., Park, D., Kim, I., Lee, S. W., Lee, W., Hwang, K. S., Lee, J. H., Lee, G., & Yoon, D. S. (2021) · Nature Communications · doi:10.1038/s41467-020-20611-4 · Cited by 33
Self-citationPaumier, J.-M., Py, N. A., García-González, L., Bernard, A., Stephan, D., Louis, L., Checler, F., Khrestchatisky, M., Baranger, K., & Rivera, S. (2019) · The FASEB Journal · doi:10.1096/fj.201801076r · Cited by 40
Bejoy, J., Song, L., Wang, Z., Sang, Q. A., Zhou, Y., & Li, Y. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00021 · Cited by 31
Implication of matrix metalloproteinases in regulating neuronal disorder
Mukherjee, A. K., & Swarnakar, S. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3752-y · Cited by 27
A Preclinical Assessment of Neural Stem Cells as Delivery Vehicles for Anti-Amyloid Therapeutics
Njie, E. G., Kantorovich, S., Astary, G. W., Green, C., Zheng, T., Semple‐Rowland, S. L., Steindler, D. A., Sarntinoranont, M., Streit, W. J., & Borchelt, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034097 · Cited by 23
“7G–I) [22].”
BackgroundMethodInfluentialYang, C.-N., Wu, M.-F., Liu, C.-C., Jung, W.-H., Chang, Y.-C., Lee, W.-P., Shiao, Y.-J., Wu, C.-L., Liou, H.-H., Lin, S.-K., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx278 · Cited by 27
Kaneko, R., Matsui, A., Watanabe, M., Harada, Y., Kanamori, M., Awata, N., Kawazoe, M., Takao, T., Kobayashi, Y., Kikutake, C., et al. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00257-7 · Cited by 30
“In situ experiments have shown that MMP-9 can degrade compact plaques of Aβ fibrils [39].”
BackgroundMendonca, P., Taka, E., Bauer, D. F., Cobourne-Duval, M. K., & Soliman, K. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.01.011 · Cited by 25
“MMP-9 can induce and degrade Aβ and compact plaques, and it is released, along with nerve growth factor precursor (pro-NGF) in an activity-dependentmanner (Yan et al., 2006).”
BackgroundStability of Aβ (1-42) peptide fibrils as consequence of environmental modifications
Gregori, M., Cassina, V., Brogioli, D., Salerno, D., Kimpe, L. D., Scheper, W., Masserini, M., & Mantegazza, F. (2010) · European Biophysics Journal · doi:10.1007/s00249-010-0619-6 · Cited by 20
Fu, H., Liu, B., Li, L., & Lemere, C. A. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.07.020 · Cited by 36
“…Chung et al., 1999; Czirr et al., 2017; Eckman et al., 2001; Farris et al., 2007; Hernandez-Guillamon et al., 2010; Leissring et al., 2003; Mandrekar et al., 2009; Melchor et al., 2003; Pacheco-Quinto and Eckman, 2013; Qiu et al., 1998; Qiu et al., 1997; Sikanyika et al., 2019; Yan et al., 2006).”
BackgroundThe Microglial Response to Neurodegenerative Disease
Song, W. M., & Colonna, M. (2018) · Advances in immunology · doi:10.1016/bs.ai.2018.04.002 · Cited by 30
Guarnieri, L., Bosco, F., Leo, A., Citraro, R., Palma, E., Sarro, G. D., & Mollace, V. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102210 · Cited by 28
“Hcy-induced neurotoxicity is due to its auto-oxidation leading to cellular oxidative stress through the formation of reactive oxygen species, neuroinflammation, and cell death (Yan et al., 2006).”
Matrix metalloproteinase‐9: A magic drug target in neuropsychiatry?
Kaczmarek, K. T., Protokowicz, K., & Kaczmarek, L. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15976 · Cited by 23
“This notion is of particular importance since inhibiting MMP-9 carries out potential risks in terms of memory impairment, or processing of the Alzheimer disease amyloid and its precursor, etc. (Yan et al., 2006; Yin et al., 2006).”
Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia
Soheili, M., Rezaei–Tavirani, M., & Salami, M. (2012) · Neuroscience & Medicine · doi:10.4236/nm.2012.34044 · Cited by 23
“Since systemic clearance of Aβ, especially by the liver, could determine the plasma levels of Aβ available for transport into the brain across the blood-brain barrier [9,15] it can be concluded that the lavender may undergo the liver clearance of Aβ.”
BackgroundIm, D., Kim, S., Yoon, G., Hyun, D. G., Eom, Y., Lee, Y. E., Sohn, C. H., Choi, J., & Kim, H. I. (2023) · JACS Au · doi:10.1021/jacsau.2c00668 · Cited by 26
Matrix Metalloproteinases in Cardioembolic Stroke: From Background to Complications
Wysocka, A., Szczygielski, J., Kopańska, M., Oertel, J., & Główniak, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043628 · Cited by 26
“Indeed, MMP-2 and -9 as well as membrane-type 1 MMP (MT1-MMP) are capable of degrading both in vitro and in vivo different forms of β-amyloid [199,200], including its vasculotropic mutants L22Q and E38V [201].”
BackgroundLinton, A. E., Weekman, E. M., & Wilcock, D. M. (2021) · Cerebral Circulation - Cognition and Behavior · doi:10.1016/j.cccb.2021.100030 · Cited by 21
Advancements in Targeting Macrophage Senescence for Age-Associated Conditions
Xiao, J., Li, H.-S., Satyanarayanan, S. K., Leung, S.-L., Yuan, Q., Wang, Y.-F., Qin, D., & Lee, S. (2024) · Aging and Disease · doi:10.14336/ad.2024.0720 · Cited by 21
“Moreover, it is involved in neuroinflammation [108], regulating BBB permeability [109] , and Aβ metabolism [110].”
Fyn Kinase in Alzheimer’s Disease: Unraveling Molecular Mechanisms and Therapeutic Implications
Meur, S., & Karati, D. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04286-2 · Cited by 24
“MMP-9 is released in an activity-dependent way together with proNGF, and it induces Aβ and causes degradation of Aβ along with compact plaques [105].”
Dorandish, S., Williams, A., Atali, S., Sendo, S., Price, D., Thompson, C., Guthrie, J. W., Heyl, D., & Evans, H. G. (2021) · Scientific Reports · doi:10.1038/s41598-021-88574-0 · Cited by 23
Pathology of Amyloid-β (Aβ) Peptide Peripheral Clearance in Alzheimer’s Disease
Tsoy, A., Umbayev, B. A., Kassenova, A., Kaupbayeva, B., & Askarova, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252010964 · Cited by 24
“Another important group of A β -degrading proteases capable of degrading monomeric and fibrillar A β structures are matrix metalloproteinases (MMPs) [133].”
BackgroundJamal, H., Raja, R., Ahmed, S., Yesiloz, G., & Ali, S. A. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.133114 · Cited by 20
Zhang, S., Cao, F., Li, W., & Abumaria, N. (2023) · Science Signaling · doi:10.1126/scisignal.ade6325 · Cited by 20
Metal Complexes as Promising Matrix Metalloproteinases Regulators
Nguyen, Y. T., Kim, N., & Lee, H. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021258 · Cited by 25
Sorrentino, S., Ascari, R., Maderna, E., Catania, M., Ghetti, B. F., Tagliavini, F., Giaccone, G., & Fede, G. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052780 · Cited by 23
“High levels of both MMPs and IIFs have been reported in the brain of AD patients [29], where they are involved in the clearance of Aβ aggregates [71,72] and the shutdown of inflammation [73].”
BackgroundHussain, A. A., Lee, Y., & Marshall, J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100775 · Cited by 26
MMP-7 cleaves amyloid β fragment peptides and copper ion inhibits the degradation
Taniguchi, M., Matsuura, K., Nakamura, R., Kojima, A., Konishi, M., & Akizawa, T. (2017) · Biometals · doi:10.1007/s10534-017-0048-4 · Cited by 20
Marine pharmacology: therapeutic targeting of matrix metalloproteinases in neuroinflammation
Gentile, E., & Liuzzi, G. M. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.09.023 · Cited by 19
Metalloproteinases and neurodegenerative diseases: pathophysiological and therapeutic perspectives
Rosenberg, G. A. (2015) · Metalloproteinases In Medicine · doi:10.2147/mnm.s68849 · Cited by 21
“Blood vessels, astrocytes, and microglia can be induced to produce MMPs by the amyloid molecules.(72) Exposure of astrocytes to Aβ 1–40 induces the secretion of MMP-2, MMP-3, and MMP-9.”
BackgroundAn aminopeptidase from Streptomyces sp. KK565 degrades beta amyloid monomers, oligomers and fibrils
Yoo, C., Ahn, K., Park, J., Kim, M.-J., & Jo, S. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.08.048 · Cited by 20
Alterations of Emotional and Cognitive Behaviors in Matrix Metalloproteinase-2 and -9-Deficient Mice
Mizoguchi, H., Ibi, D., Takuma, K., Kitahara, Y., Tóth, E., Sato, J., Itohara, S., Nabeshima, T., & Yamada, K. (2010) · The Open Behavioral Science Journal · doi:10.2174/1874230001004010019 · Cited by 20
“For example, MMP-9 degrades β-amyloid (Aβ) and amyloid plaques [5], and has been implicated specifically in cerebral ischemia [6], kainate-induced neuronal injury [7], and hippocampal long-term potentiation (LTP) and memory [8].”
BackgroundKoca, S., Kiris, İ., Şahin, Ş., Çınar, N., Karşıdağ, S., Hanağası, H. A., Yıldız, G. B., & Baykal, A. T. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.136799 · Cited by 23
Late Passage Cultivation Induces Aged Astrocyte Phenotypes in Rat Primary Cultured Cells
Bang, M., Gonzales, E. L., Shin, C. Y., & Kwon, K. J. (2021) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2020.175 · Cited by 19
“Microglia and astrocytes can generate A degrading proteases such as neprilysin (NEP), endothelin-converting enzyme (ECE), cathepsin B (CAT-B), and matrix metalloproteases (MMPs) (Eckman et al., 2001, 2003; Yan et al., 2006; Yin et al., 2006; Halle et al., 2008).”
BackgroundRollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer’s disease
Sharma, R., Razdan, K., Bansal, Y., & Kuhad, A. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1524877 · Cited by 22
“They have been found to mediate Aβ formation and clearance [75] and are also induced by Aβ in microglia, astrocytes, and blood vessels [76].”
BackgroundRichman, M., Perelman, A., Gertler, A. A., & Rahimipour, S. (2012) · Biomacromolecules · doi:10.1021/bm301401b · Cited by 15
Ganguly, K., Adhikary, K., Acharjee, A., Acharjee, P., Trigun, S. K., Mutlaq, A. S., Ashique, S., Yasmin, S., Alshahrani, A. M., & Ansari, M. Y. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135967 · Cited by 23
Proust, A. M., Barat, C., Lebœuf, M., Drouin, J., Gagnon, M., Vanasse, F., & Tremblay, M. J. (2020) · Glia · doi:10.1002/glia.23833 · Cited by 19
“role in extracellular degradation of both soluble and fibrillary forms of Aβ (Yan et al., 2006; Yin et al., 2006).”
BackgroundHussain, A. A., Lee, Y., Zhang, J.-J., Francis, P. T., & Marshall, J. (2017) · Journal of Neurodegenerative Diseases · doi:10.1155/2017/4810232 · Cited by 20
Neuron–microglia interactions in neuroinflammation
Mizuno, T. (2015) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12228 · Cited by 22
Schilling, S., Pradhan, A., Heesch, A., Helbig, A., Blennow, K., Koch, C., Bertgen, L., Koo, E. H., Brinkmalm, G., Zetterberg, H., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01577-y · Cited by 21
“On the other hand, Matrix Metalloproteinase 9 (MMP9) was reported to generate different C-terminally truncated Aβ fragments, including Aβ1–16, Aβ1–20, Aβ1–23, Aβ1–30, Aβ1–33 and Aβ1–34 [82, 83].”
Experimental approaches for altering the expression of Abeta‐degrading enzymes
Loeffler, D. A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15762 · Cited by 18
“MMP- 9 and MT1- MMP also cleave fibrillar Aβ (Hernandez- Guillamon et al., 2015; Liao & Van Nostrand, 2010; White et al., 2006; Yan et al., 2006).”
BackgroundBrzdąk, P., Nowak, D., Wiera, G., & Mozrzymas, J. W. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00178 · Cited by 21
“However, other MT1-MMP cleavage sites were identified in the region between V12 and L17 that are similar to the sequences that are cleaved by IDE (e.g., H14-Q16, Q16-K16; Yan et al., 2006; Liao and Van Nostrand, 2010).”
BackgroundInfluentialBarage, S. H., Jalkute, C. B., Dhanavade, M. J., & Sonawane, K. D. (2014) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-014-9403-2 · Cited by 16
“Keywords AD (Alzheimer’s disease) Ab (amyloid beta peptide) hECE-1 (human endothelin converting enzyme) Molecular docking Molecular dynamics (MD) simulation”
BackgroundZara, S., Rapino, M., Sozio, P., Stefano, A. D., Nasuti, C., & Cataldi, A. (2011) · Brain Research · doi:10.1016/j.brainres.2011.07.022 · Cited by 17
Porter, K. N., Sarkar, S. N., Dakhlallah, D. A., Vannoy, M. E., Quintana, D. D., & Simpkins, J. W. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00092 · Cited by 17
“In contrast to other Aβ-degrading proteases, MMP-9 is known to degrade Aβ fibrils in vitro, Aβ plaques in situ, and Aβ in vivo (Backstrom et al., 1996; Yan et al., 2006; Yin et al., 2006; Hernandez-Guillamon et al., 2015).”
BackgroundResultInfluentialSex-specific associations of matrix metalloproteinases in Alzheimer’s disease
Aksnes, M., Edwin, T. H., Saltvedt, I. T., Eldholm, R. S., Chaudhry, F. A., Halaas, N. B., Myrstad, M., Watne, L. O., & Knapskog, A. (2023) · Biology of Sex Differences · doi:10.1186/s13293-023-00514-x · Cited by 20
“Indeed, MMPs are involved in Aβ degradation [11, 12], and MMPs have been found expressed in Aβ plaques [13, 14].”
BackgroundMatrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals.
Aksnes, M., Capogna, E., Vidal-Piñeiro, D., Chaudhry, F., Myrstad, M., Idland, A., Halaas, N., Dakhil, S., Blennow, K., Zetterberg, H., et al. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.05.012 · Cited by 16
Brezováková, V., Syková, E., & Jadhav, S. (2022) · Cells · doi:10.3390/cells11091429 · Cited by 19
“Cells 2022, 11, 1429 18 of 23 It is suggested that MMP-2 and MMP-9 are involved in the degradation of Aβ into nontoxic fragments and exert protective effect on neurons in AD [61].”
BackgroundInfluentialOverlapping Protein Accumulation Profiles of CADASIL and CAA
Young, K. Z., Xu, G., Keep, S. G., Borjigin, J., & Wang, M. M. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.11.015 · Cited by 24
Microglia in Alzheimer’s Disease
Süß, P., & Schlachetzki, J. C. M. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200212155234 · Cited by 26
Fukui, K., Yachi, K., Yoshida, H., Tanji, K., Matsumiya, T., Hayakari, R., Tsuruga, K., Tanaka, H., & Imaizumi, T. (2017) · Neurosciences research · doi:10.1016/j.neures.2017.05.005 · Cited by 16
Patel, A., Vasanthan, V., Fu, W., Fahlman, R. P., MacTavish, D., & Jhamandas, J. H. (2015) · Brain Structure and Function · doi:10.1007/s00429-015-1007-x · Cited by 19
“Since MMP-9 is capable of cleaving A b (1-40) at the same site as a -secretase, between Lys-16 and Leu-17, astrocytic and neuronal release of MMPs may serve as a compensatory and neuroprotective measure to attenuate A b toxicity (Yan et al. 2006).”
InfluentialThe Nuclear Inclusion a (NIa) Protease of Turnip Mosaic Virus (TuMV) Cleaves Amyloid-β
Han, H.-E., Sellamuthu, S., Shin, B. H., Lee, Y., Song, S., Seo, J.-S., Baek, I., Bae, J., Kim, H., Yoo, Y. J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015645 · Cited by 15
Alzheimer’s Disease: Models and Molecular Mechanisms Informing Disease and Treatments
Nystuen, K., McNamee, S. M., Akula, M., Holton, K. M., DeAngelis, M. M., & Haider, N. B. (2024) · Bioengineering · doi:10.3390/bioengineering11010045 · Cited by 28
An inorganic overview of natural Aβ fragments: Copper(II) and zinc(II)-mediated pathways
Lanza, V., Bellia, F., & Rizzarelli, E. (2018) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2018.04.004 · Cited by 18
Daschil, N., & Humpel, C. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00075 · Cited by 18
Li, X., Yuan, H.-F., Quan, Q.-K., Wang, J.-J., Wang, N.-N., & Li, M. (2011) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-011-0896-7 · Cited by 15
Chavoshinezhad, S., Beirami, E., & Izadpanah, E. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118568 · Cited by 15
Empirical study using network of semantically related associations in bridging the knowledge gap
Abedi, V., Yeasin, M., & Zand, R. (2014) · Journal of Translational Medicine · doi:10.1186/s12967-014-0324-9 · Cited by 14
“In fact MMP proteins can breakdown the amyloid proteins [26] that are present in the brain of the AD patients.”
BackgroundRefining the interactions between microglia and astrocytes in Alzheimer’s disease pathology
Chen, J., Xu, S., Wang, L., Liu, X., Liu, G., Tan, Q., Li, W., Zhang, S., & Du, Y. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.03.033 · Cited by 17
Amontree, M., Nelson, M., Stefansson, L., Pak, D. T. S., Maguire-Zeiss, K., Turner, R., & Conant, K. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16031 · Cited by 13
“For example, MMP-9 is an α - secretase that can also degrade fibrillar amyloid (Backstrom et al., 1996 ; Yan et al., 2006 ).”
Yoon, M., Kim, H., Shin, H., Lee, H., Kang, M., Park, S., Han, G., Kim, Y. S., & Choi, K. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106836 · Cited by 15
Yousefizadeh, A., Piccioni, G., Saidi, A., Triaca, V., Mango, D., & Nisticò, R. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106404 · Cited by 15
Key Enzymes and Proteins in Amyloid-Beta Production and Clearance
Santos, C. R. A., Cardoso, I., & Gonçalves, I. (2011) · InTech eBooks · doi:10.5772/17646 · Cited by 5
“MMP-9 Hydrolises peptide bonds of A┚40 and A┚42 and aggregated A┚ fibrils Neurons, endothelial cells (Miners et al. 2008a; Yan et al. 2006)”
BackgroundHuang, L., Liu, M., Li, Z., Li, B., Wang, J., & Zhang, K. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00865 · Cited by 13
“We speculate that MMP-9 may be upregulated as a protective mechanism during the AD-related MCI stage of pathogenesis, potentially because MMP-9 can degrade both soluble and insoluble forms of Aβ (Yan et al., 2006; Merlo et al., 2012; Liu et al., 2023).”
Plasma MMP-9/TIMP-1 ratio serves as a novel potential biomarker in Alzheimer’s disease
Liu, J., Li, X., & Qu, J. (2023) · Neuroreport · doi:10.1097/wnr.0000000000001952 · Cited by 21
Solving the Amyloid Paradox: Unveiling the Complex Pathogenicity of Amyloid Fibrils
Sulatsky, M. I., Stepanenko, O. V., Stepanenko, O. V., & Sulatskaya, A. I. (2025) · Aggregate · doi:10.1002/agt2.70078 · Cited by 9
“These include chaperone disaggregase complexes [144] and various enzymes: matrix metalloproteinases (MMPs) [145–149], disintegrin and metalloproteinase domain-containing protein adm-2 [150], trypsin [151–153], high temperature requirement a serine peptidase 1 (HTRA1) [154] and lysosomal proteases…”
The Common Alzheimer's Disease Research Ontology (CADRO) for biomarker categorization
Osse, A. M. L., Kinney, J. W., & Cummings, J. L. (2025) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70050 · Cited by 7
Vervuurt, M., de Kort, A. D., Jäkel, L., Kersten, I., Abdo, W. F., Schreuder, F., Rasing, I., Terwindt, G., Wermer, M., Greenberg, S., et al. (2023) · Alzheimer's Research & Therapy · doi:10.1186/s13195-023-01171-3 · Cited by 11
Potent therapeutic targets for treatment of Alzheimer's disease: Amyloid degrading enzymes
Choi, H. S., Kim, E., Choi, J. Y., Park, E., & Lee, H. J. (2021) · Bulletin of the Korean Chemical Society · doi:10.1002/bkcs.12390 · Cited by 11
Amyloid beta peptide-degrading microbial enzymes and its implication in drug design
Dhanavade, M. J., & Sonawane, K. D. (2020) · 3 Biotech · doi:10.1007/s13205-020-02240-2 · Cited by 16
Leite, J. P., & Gales, L. (2018) · FEBS Letters · doi:10.1002/1873-3468.13285 · Cited by 12
Downsizing of Lean Body Mass is a Key Determinant of Alzheimer's Disease
Ingenbleek, Y., & Bernstein, L. H. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141950 · Cited by 9
“dation of A 1-40 [74] and A 1–42 [77] peptides.”
The ageing immune system and its clinical implications
Wordsworth, D., & Dunn‐Walters, D. K. (2010) · Reviews in Clinical Gerontology · doi:10.1017/s0959259810000407 · Cited by 9
Greco, G. A., Rock, M. B., Amontree, M., Lanfranco, M. F., Korthas, H. T., Hong, S. H., Turner, R. S., Rebeck, G. W., & Conant, K. E. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106057 · Cited by 11
“Similar to select ADAMs, MMP-9 acts as an α-secretase and is also one of the few proteases that can also degrade fibrillar amyloid (Yan et al., 2006; Yin et al., 2006).”
Sasaki, Y., Kimura, N., Aso, Y., Yabuuchi, K., Aikawa, M., & Matsubara, E. (2021) · Biomolecules · doi:10.3390/biom11101496 · Cited by 11
Li, S.-J., Liu, Q., He, X., Liu, J., Liu, X., Hu, J., Tang, Z., Peng, Q., Cui, L.-J., Zhang, H.-N., et al. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.126858 · Cited by 9
Saleh, S. Y., Sadeghi, L., & Dehghan, G. (2024) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2024-2486 · Cited by 7
“Previ‑ ous studies have confirmed that brain tissue has an ef‑ fective endogenous system, including MMP‑9, MMP‑3, NEP, and IDE (Wei et al., 1991; Yan et al., 2006; Kim et al., 2010; Hafez et al., 2011; Pivovarova et al., 2016), to degrade extra Aβ and deposited fibrils.”
BackgroundInfluentialThe Implication of Glial Metabotropic Glutamate Receptors in Alzheimer’s Disease
de Lima, I. B. Q., & Ribeiro, F. M. (2021) · Current Neuropharmacology · doi:10.2174/1570159x20666211223140303 · Cited by 9
“Astrocytes can produce proteases that degrade Aβ, such as matrix metalloproteinases 2 and 9, whose expression is increased in reactive astrocytes near Aβ plaques in aged APP/PS1 mice [173, 174].”
Soria-Tobar, L., Román-Valero, L., Sebastián‐Serrano, Á., Aivar, P., Alvarez‐Castelao, B., & Dı́az-Hernández, M. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01600-x · Cited by 8
“Given that MMP9 can degrade amyloid-β-fibrils from compact plaques in APP/PS1 + / − mice [48], the inability of levamisole to prevent the reduced MMP9 expression in APP/PS1 + / − mice might underlie this unexpected result.”
BackgroundGardner, R. S., Kyle, M. M., Hughes, K., & Zhao, L. (2024) · Biomolecules · doi:10.3390/biom14070827 · Cited by 7
“Individual cells in cluster 14 co-express”
Futai, E., Kawasaki, H., Sato, S., Daoudi, K., Hidaka, M., Tomita, T., & Ogawa, T. (2023) · Toxins · doi:10.3390/toxins15080500 · Cited by 8
“MMP9 reduced the ThT signal significantly after 5 days [30] and myeline basic protein after 2 days [32].”
BackgroundKurronen, A., Pihlaja, R., Pollari, E., Kanninen, K. M., Storvik, M., Wong, G., Koistinaho, M., & Koıstınaho, J. (2012) · World Journal of Neuroscience · doi:10.4236/wjns.2012.22009 · Cited by 6
“Interestingly, Mmp9, a peptidase capable of degrading Aβ fibrils [46], was expressed at over two fold higher levels in neonatal astrocytes compared to adult astrocytes, although neonatal astrocytes do not possess Aβ degrading or clearing capacity ex vivo.”
BackgroundIemmolo, M., Bivona, G., Piccoli, T., Nicosia, A., Schiera, G., Liegro, C. M. D., Pietra, F. D., & Ghersi, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052510 · Cited by 6
The Potential Use of Matrix Metalloproteinases in Alzheimer’s Disease Therapy
Krawczuk, D., & Mroczko, B. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15041555 · Cited by 3
Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation
Danhash, E., Verbeck, A. C., Western, D., Díaz‐Pacheco, A. S., Galasso, G., You, S., Huang, G., Starr, E., Miller, N., Nadarajah, C. J., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70580 · Cited by 6
Self-citationPeng, M., Zeng, Q., Zheng, W., & Xia, X.-B. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05078-y · Cited by 4
“AD, Alzheimer’s disease; AMD, age-related macular degeneration; MR, macular retina; MCRS, macular choroid/RPE/sclera; PR, peripheral retina; PCRS, peripheral choroid/RPE/sclera; DEGs, differentially expressed genes barrier [41] and contributes to senile plaque formation [42].”
Degradation of pathogenic amyloids induced by matrix metalloproteinase-9
Stepanenko, O. V., Sulatsky, M. I., Mikhailova, E. V., Stepanenko, O. V., & Sulatskaya, A. I. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136362 · Cited by 3
Mori, N., & Mook-Jung, I. (2015) · Springer Japan · doi:10.1007/978-4-431-55763-0 · Cited by 4
Kawano, R., Nakanishi, A., Zako, T., & Shimazaki, Y. (2019) · Separation Science Plus · doi:10.1002/sscp.201900049 · Cited by 3
The NGF Metabolic Pathway: New Opportunities for Biomarker Research and Drug Target Discovery
Pentz, R., & Iulita, M. F. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-74046-7_4 · Cited by 7
Literature Mining and Ontology Mapping Applied to Big Data
Abedi, V., Yeasin, M., & Zand, R. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801967-2.00013-6 · Cited by 3
Combating ageing beyond the cell: Emerging roles of extracellular proteostasis
Venkatesh, S. R., Gallotta, I., Olabiyi, B. F., Choi, Y. H., Inglesfield, S., Kumita, J. R., Ewald, C. Y., & David, D. C. (2026) · FEBS Journal · doi:10.1111/febs.70647 · Cited by 2
“Evidence with aged AD mouse brain slices shows that MMP9 can degrade compact amyloid plaques [160].”
Ng, B., Kodosaki, E., Veleva, E., Keshavan, A., Schott, J. M., Heslegrave, A., Fox, N. C., & Zetterberg, H. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71082 · Cited by 3
“Previous reports demonstrated that the expression of MMP-9, which belongs to the same MMP family as MMP-10, can be induced by A b and in turn results in A b degradation 36,37 .”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
