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.
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
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?
MMP-9 is capable of degrading amyloid fibrils in vitro and amyloid plaques in situ.
“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]
Expression of MMP-9 is up-regulated in reactive astrocytes surrounding plaques.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
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 · see citing works
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 · see citing works
Common core structure of amyloid fibrils by synchrotron X-ray diffraction.
Sunde, M., Serpell, L., Bartlam, M., Fraser, P., Pepys, M., & Blake, C. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1348 · Cited by 1,666 · see citing works
Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E., Frosch, M., Eckman, C., Tanzi, R., Selkoe, D., & Guénette, S. (2003) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0230450100 · Cited by 1,361 · see citing works
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 · see citing works
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 · see citing works
Alzheimer's amyloid fibrils: structure and assembly.
Serpell, L. (2000) · Biochimica et Biophysica Acta · doi:10.1016/s0925-4439(00)00029-6 · Cited by 922 · see citing works
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 · see citing works
Metabolic Regulation of Brain Aβ by Neprilysin
Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N., Gerard, C., Hama, E., Lee, H., & Saido, T. (2001) · Science · doi:10.1126/science.1059946 · Cited by 894 · see citing works
Iwata, N., Tsubuki, S., Takaki, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., Kawashima-Morishima, M., Lee, H.-J., Hama, E., Sekine-Aizawa, Y., et al. (2000) · Nature Medicine · doi:10.1038/72237 · Cited by 867 · see citing works
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571 · see citing works
Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease
Nagele, R. G., Węgiel, J., Venkataraman, V., Imaki, H., Wang, K.-C., & Wegiel, J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.01.007 · Cited by 497 · see citing works
Bacskai, B. J., Kajdasz, S. T., Christie, R. H., Carter, C., Games, D., Seubert, P. A., Schenk, D., & Hyman, B. T. (2001) · Nature Medicine · doi:10.1038/85525 · Cited by 445 · see citing works
Gu, Z., Cui, J.-K., Brown, S. M., Fridman, R., Mobashery, S., Strongin, A., & Lipton, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1563-05.2005 · Cited by 412 · see citing works
Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C. L., & Beyreuther, K. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90835-8 · Cited by 402 · see citing works
Kurochkin, I. V., & Goto, S. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00387-4 · Cited by 401 · see citing works
Rosenberg, G. A., Cunningham, L. A., Wallace, J., Alexander, S., Estrada, E. Y., Grossetete, M., Razhagi, A., Miller, K., & Gearing, A. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03294-7 · Cited by 388 · see citing works
HIGH-RESOLUTION ELECTRON MICROSCOPIC ANALYSIS OF THE AMYLOID FIBRIL
Shirahama, T., & Cohen, A. B. (1967) · Journal of Cell Biology · doi:10.1083/jcb.33.3.679 · Cited by 361
Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme*
Eckman, E., Reed, D. K., & Eckman, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007579200 · Cited by 345 · see citing works
Backstrom, J. R., Lim, G. P., Cullen, M. J., & Tökés, Z. A. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-24-07910.1996 · Cited by 331 · see citing works
Hu, J.-G., Igarashi, A., Kamata, M., & Nakagawa, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104068200 · Cited by 307 · see citing works
The Plasmin System Is Induced by and Degrades Amyloid-β Aggregates
Tucker, H. M., Kihiko‐Ehmann, M., Caldwell, J. N., Wright, S., Kawarabayashi, T., PRICE, D. A., Walker, D., Scheff, S. W., McGillis, J. P., Rydel, R. E., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-11-03937.2000 · Cited by 306 · see citing works
Hyman, B., Marzloff, K., & Arriagada, P. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199311000-00006 · Cited by 294 · see citing works
The Profile of Soluble Amyloid β Protein in Cultured Cell Media
Wang, R., Sweeney, D. A., Gandy, S., & Sisodia, S. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.31894 · Cited by 293 · see citing works
Alzheimer's Disease β-Amyloid Peptide Is Increased in Mice Deficient in Endothelin-converting Enzyme
Eckman, E. A., Watson, M., Marlow, L. A., Sambamurti, K., & Eckman, C. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200642200 · Cited by 263 · see citing works
Inouye, H., Fraser, P., & Kirschner, D. (1993) · Biophysical Journal · doi:10.1016/s0006-3495(93)81393-6 · Cited by 239 · see citing works
Review: Modulating Factors in Amyloid-β Fibril Formation
McLaurin, J., Yang, D.-S., Yip, C. M., & Fraser, P. E. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4289 · Cited by 217 · see citing works
Howell, S. W., Nalbantoglu, J. N., & Crine, P. (1995) · Peptides · doi:10.1016/0196-9781(95)00021-b · Cited by 204 · see citing works
Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin.
Betsuyaku, T., Fukuda, Y., Parks, W. C., Shipley, J., & Senior, R. M. (2000) · American Journal of Pathology · doi:10.1016/s0002-9440(10)64563-4 · Cited by 203 · see citing works
Christie, R. H., Bacskai, B. J., Zipfel, W. R., Williams, R. M., Kajdasz, S. T., Webb, W. W., & Hyman, B. T. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-03-00858.2001 · Cited by 197 · see citing works
Role of matrix metalloproteinases in asthma
Kelly, E., & Jarjour, N. (2003) · Current opinion in pulmonary medicine · doi:10.1097/00063198-200301000-00005 · Cited by 165 · see citing works
Residues 17–20 and 30–35 of beta‐amyloid play critical roles in aggregation
Liu, R., McAllister, C., Lyubchenko, Y. L., & Sierks, M. R. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10859 · Cited by 165 · see citing works
Lorenzl, S., Albers, D. S., LeWitt, P., Chirichigno, J. W., Hilgenberg, S. L., Cudkowicz, M., & Beal, M. (2003) · Journal of Neurological Sciences · doi:10.1016/s0022-510x(02)00398-2 · Cited by 162 · see citing works
Amyloid Fibril Toxicity in Alzheimer's Disease and Diabetes a
Lorenzo, A., & Yankner, B. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34406.x · Cited by 162 · see citing works
Molecular Structure of a Fibrillar Alzheimer's Aβ Fragment†
Serpell, L., Blake, C., & Fraser, P. (2000) · Biochemistry · doi:10.1021/bi000637v · Cited by 148 · see citing works
Sun, A.-Y., Nguyen, X. V., & Bing, G. (2002) · Journal of Histochemistry and Cytochemistry · doi:10.1177/002215540205000403 · Cited by 146 · see citing works
Ideas of order for amyloid fibril structure.
Wetzel, R. (2002) · Structure · doi:10.1016/s0969-2126(02)00809-2 · Cited by 144 · see citing works
Atwood, C., Martins, R. N., Smith, M. A., & Perry, G. L. (2002) · Peptides · doi:10.1016/s0196-9781(02)00070-0 · Cited by 137 · see citing works
Levine, H. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0137 · Cited by 126
Aggregation and disaggregation of senile plaques in Alzheimer disease
Cruz, L., Urbanc, B., Buldyrev, S. V., Christie, R. H., Gómez‐Isla, T., Havlin, S., McNamara, M. J., Stanley, E., & Hyman, B. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7612 · Cited by 115 · see citing works
Lee, J., Yin, K., Hsin, I., Chen, S.-W., Fryer, J., Holtzman, D., Hsu, C. Y., & Xu, J. (2003) · Annals of Neurology · doi:10.1002/ana.10671 · Cited by 110 · see citing works
Self-citationGoussev, S., Hsu, J.-Y. C., Lin, Y., Tjoa, T., Maida, N., Werb, Z., & Noble-Haeusslein, L. (2003) · Journal of Neurosurgery · doi:10.3171/spi.2003.99.2.0188 · Cited by 102 · see citing works
Maier, C. M., Hsieh, L. B., Yu, F.-S., Bracci, P., & Chan, P. H. (2004) · Stroke · doi:10.1161/01.str.0000125861.55804.f2 · Cited by 85 · see citing works
Morelli, L., Llovera, R., González, S., Affranchino, J. L., Prelli, F., Frangione, B., Ghiso, J., & Castaño, E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300276200 · Cited by 84 · see citing works
β-Amyloid induces the production of active, matrix-degrading proteases in cultured rat astrocytes
Deb, S., Zhang, W.-J. J., & Gottschall, P. E. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02344-8 · Cited by 76 · see citing works
Glucocorticoid Receptor Expression in the Spinal Cord after Traumatic Injury in Adult Rats
Yan, P., Xu, J., Li, Q., Chen, S., Kim, G.-M., Hsu, C. Y., & Xu, X. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09355.1999 · Cited by 73 · see citing works
Self-citationBerman, N. E., Marcario, J., Yong, C., Raghavan, R., Raymond, L., Joag, S. V., Narayan, O., & Cheney, P. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0261 · Cited by 64 · see citing works
An intersheet packing interaction in A beta fibrils mapped by disulfide cross-linking.
Shivaprasad, S., & Wetzel, R. (2004) · Biochemistry · doi:10.1021/bi048019s · Cited by 56 · see citing works
Thal, D. R., Arendt, T., Waldmann, G., Holzer, M., Zedlick, D., Rüb, U., & Schober, R. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00090-6 · Cited by 53 · see citing works
Osler and the "medico-chirurgical neurologists": Horsley, Cushing, and Penfield.
Feindel, W. (2003) · Journal of Neurosurgery · doi:10.3171/jns.2003.99.1.0188 · Cited by 53 · see citing works
Bond, J. P., Deverin, S. P., Inouye, H., El‐Agnaf, O. M. A., Teeter, M. M., & Kirschner, D. A. (2003) · Journal of Structural Biology · doi:10.1016/s1047-8477(02)00625-1 · Cited by 49 · see citing works
Zhang, X., Cheng, M., & Chintala, S. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.10.084 · Cited by 38
Flagged first, then by citations
5 of the 58 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Cruz, L., Urbanc, B., Buldyrev, S. V., Christie, R., Gomez-Isla, T., Havlin, S., McNamara, M., Stanley, H. E., and Hyman, B. T. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 7612-7616
- Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E. A., Frosch, M. P., Eckman, C. B., Tanzi, R. E., Selkoe, D. J., and Guenette, S. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 4162-4167
Cited by
Sorted by citations
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329 · see citing works
“In addition to their ability to phagocytose A , microglia can also clear A by degradation via A -degrading enzymes (Leissring et al., 2003; Yan et al., 2006).”
Astrocytes: a central element in neurological diseases
Pekny, M., Pekna, M., Messing, A., Steinhäuser, C., Lee, J., Parpura, V., Hol, E. M., Sofroniew, M. V., & Verkhratsky, A. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1513-1 · Cited by 755 · see citing works
Self-citationMatrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers
Rempe, R. G., Hartz, A. M. S., & Bauer, B. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16655551 · Cited by 784 · see citing works
“While MMPs might be involved in processing Ab and clearing plaques, they are likely not major players in this process.(219,229) Thus, MMPs are increased in the AD brain, but the role of MMPs in AD is unknown.”
BackgroundInfluentialFunction and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625 · see citing works
Matrix metalloproteinases and their multiple roles in neurodegenerative diseases
Rosenberg, G. A. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70016-x · Cited by 594 · see citing works
Mechanisms of Aβ Clearance and Degradation by Glial Cells
Ries, M., & Sastre, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00160 · Cited by 527 · see citing works
“Matrix metalloproteinases, known to be expressed and secreted by astrocytes, play a role in the extracellular degradation of both monomeric and fibrillar forms of Aβ (Yan et al., 2006).”
BackgroundGonzález-Reyes, R. E., Nava-Mesa, M. O., Vargas-Sánchez, K., Ariza-Salamanca, D. F., & Mora-Muñoz, L. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00427 · Cited by 525 · see citing works
“Astrocytes also express and secrete several MMPs, including MMP-2 and MMP-9, which degrade both monomeric and fibrillar extracellular forms of A β (Ries and Sastre, 2016).”
BackgroundMueller-Steiner, S., Zhou, Y.-G., Arai, H., Roberson, E., Sun, B.-G., Chen, J., Wang, X., Yu, G.-Q., Esposito, L., Mucke, L., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.027 · Cited by 466 · see citing works
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
De Strooper, B. (2010) · Physiological Reviews · doi:10.1152/physrev.00023.2009 · Cited by 455 · see citing works
Elusive roles for reactive astrocytes in neurodegenerative diseases
Ben Haim, L., Carrillo-de Sauvage, M.-A., Ceyzériat, K., & Escartin, C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00278 · Cited by 453 · see citing works
Cauwe, B., den Steen, P. E. V., & Opdenakker, G. (2007) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230701340019 · Cited by 384 · see citing works
“Furthermore, MMP-9 is expressed in astrocytes surrounding plaques in the brains of aged APP/PS1 mice, and its activity is specifically detected in compact plaques (Yan et al., 2006).”
BackgroundMMP ‐9 in translation: from molecule to brain physiology, pathology, and therapy
Vafadari, B., Salamian, A., & Kaczmarek, L. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13415 · Cited by 381 · see citing works
“Moreover, Yan et al. (2006) reported that MMP-9 can degrade aggregated Ab fibrils and that the enzyme is induced by the presence of Ab, especially in reactive astrocytes that surround amyloid plaque.”
BackgroundProteolytic Degradation of Amyloid -Protein
Saido, T., & Leissring, M. A. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006379 · Cited by 368 · see citing works
Astrocyte Biomarkers in Alzheimer’s Disease
Carter, S. F., Herholz, K., Rosa-Neto, P., Pellerin, L., Nordberg, A., & Zimmer, E. R. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.11.006 · Cited by 355 · see citing works
Sharma, P., Srivastava, P., Seth, A., Tripathi, P. N., Banerjee, A. G., & Shrivastava, S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.006 · Cited by 331 · see citing works
Amyloid-Beta Protein Clearance and Degradation (ABCD) Pathways and their Role in Alzheimer’s Disease
Baranello, R., Bharani, K., Padmaraju, V., Chopra, N., Lahiri, D., Greig, N., Pappolla, M., & Sambamurti, K. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666141218140953 · Cited by 331 · see citing works
“When compared to other degrading proteases, such as ECE, IDE, and NEP, MMP-9 was found to be unique in its ability to degrade A fibrils in vitro and within compact plaques in situ, liberating A fragments 1-20 and 1-30 by cleaving sites within the hairpin loop formation of the sheet structure [186, 188].”
BackgroundAttenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice
Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-208660 · Cited by 324 · see citing works
“astrocytes surrounding plaques (61, 62) and that”
Self-citationLee, J. K., Jin, H. K., Endo, S., Schuchman, E. H., Carter, J., & Bae, J.-S. (2009) · Stem Cells · doi:10.1002/stem.277 · Cited by 303 · see citing works
Self-citationThe identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
Huang, H.-C., & Jiang, Z.-F. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-0960 · Cited by 278 · see citing works
“…neprilysin(NEP) [25,26],endothelincon-verting enzyme (ECE)-1 [27], insulin degrading enzyme (IDE) [28,29], angiotensin converting enzyme (ACE) [30], cathepsin D [31], gelatinase A [32], matrix metalloendopeptidase-9 (MMP-9) [33], coagulation factor XIa [34] and α 2-macroglobulin complexes [35].”
Lee, H. J., Lee, J. K., Lee, H.-W., Carter, J., Chang, J. W., Oh, W., Yang, Y. S., Suh, J., Lee, B., Jin, H. K., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.03.024 · Cited by 284 · see citing works
“Microglia secrete proteolytic enzymes that degrade A , such as IDE (insulin-degrading enzyme), NEP (neprilysin), MMP-9 (matrix metalloproteinase 9), and plasminogen (Leissring et al., 2003; Yan et al., 2006).”
BackgroundSelf-citationClearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes
Zuroff, L. R., Daley, D. A., Black, K. L., & Koronyo‐Hamaoui, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2463-7 · Cited by 275 · see citing works
“MMP-9 has been shown to degrade compact plaques [186, 187] as well as soluble Aβ42 and Aβ40 [167].”
BackgroundAβ-degrading enzymes: potential for treatment of Alzheimer disease
Miners, J. S., Barua, N., Kehoe, P. G., Gill, S., & Love, S. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182345e46 · Cited by 265 · see citing works
“The levels of several other candidate AA-degrading proteases, namely, ECE-2 (31), MMP-2 and MMP-9 (64, 173), CTSB (32, 174, 175), and APEH (70), were reported to be elevated in AD; however, in other studies, the concentrations and activities of MMP-2, MMP-3, MMP-9, and plasmin were not increased (120, 124).”
BackgroundInfluentialSbardella, D., Fasciglione, G., Gioia, M., Ciaccio, C., Tundo, G., Marini, S., & Coletta, M. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.015 · Cited by 247 · see citing works
Targeting the neural extracellular matrix in neurological disorders
Soleman, S., Filippov, M. A., Dityatev, A., & Fawcett, J. W. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.050 · Cited by 244 · see citing works
“Importantly, MMP-9 degrades Ab fibrils in vitro or in compact plaques in situ (Yan et al., 2006).”
BackgroundCombined Angiotensin Receptor Antagonism and Neprilysin Inhibition
Hubers, S. A., & Brown, N. (2016) · Circulation · doi:10.1161/circulationaha.115.018622 · Cited by 232 · see citing works
“The mechanisms of action of ARBs such as valsartan have been studied extensively, are reviewed elsewhere, and are not addressed in detail here.(4) In brief, ARBs decrease vasoconstriction and aldosterone production and increase natriuresis by gest on July (2)2, 2018 http://ciajournals.”
BackgroundGelatinase B/MMP-9 in Tumour Pathogenesis and Progression
Farina, A., & Mackay, A. (2014) · Cancers · doi:10.3390/cancers6010240 · Cited by 213 · see citing works
“substrates, both old and new, we direct reader to the following articles [52,55–118].”
BackgroundBrkic, M., Balusu, S., Libert, C., & Vandenbroucke, R. E. (2015) · Mediators of Inflammation · doi:10.1155/2015/620581 · Cited by 205 · see citing works
Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease
Yoon, S.-S., & AhnJo, S.-M. (2012) · Biomolecules and Therapeutics · doi:10.4062/biomolther.2012.20.3.245 · Cited by 205 · see citing works
“The levels of ECE-1 (Wang et al., 2009a), ECE-2 (Palmer et al., 2009), MMP-2 (Yan et al., 2006), MMP3, MMP-9 (Bruno et al., 2009) and ACE-2 were reported to increase in AD, but other studies showed no alterations in those of MMP-2, MMP-3, and MMP-9 (Baig et al., 2008).”
ResultMultifaceted role of matrix metalloproteinases (MMPs)
Singh, D., Srivastava, S., Chaudhuri, T., & Upadhyay, G. (2015) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2015.00019 · Cited by 194 · see citing works
“At one hand it directly degrade Aβ resulting in reduction in Aβ deposit (Yan et al., 2006; Miners et al., 2008); then again, these could contribute to brain parenchymal destruction when induced by Aβ in microglia, astrocytes or vascular smooth muscle cells.”
BackgroundCheng, Y., Tian, D., & Wang, Y.-J. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00195-1 · Cited by 195 · see citing works
“In addition, ECE-1, plasmin, and MMP-9 also participate in Aβ degradation [58, 59], and compelling data support a major role of MMP-9 in the degradation of Aβ compact plaques [60, 61], demonstrating its potent role in Aβ clearance.”
Tudorache, I. F., Trusca, V. G., & Gafencu, A. V. (2017) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2017.05.003 · Cited by 186 · see citing works
“pression, can be correlated with AD pathogenesis [81].”
BackgroundBjerke, M., Zetterberg, H., Edman, Å., Blennow, K., Wallin, A., & Andreasson, U. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110566 · Cited by 180 · see citing works
“also been shown to be induced by A [24–27] and furthermore MMP−2, −3 and −9 are all able to degrade A in vitro [28, 29].”
Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810572 · Cited by 204 · see citing works
Are amyloid‐degrading enzymes viable therapeutic targets in Alzheimer’s disease?
Nalivaeva, N., Beckett, C. S., Belyaev, N. D., & Turner, A. J. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07510.x · Cited by 178 · see citing works
“…and, of these, MMP-2, -3, -6 and -9 have been reported to degrade Ab1-40, although most attention has focused on MMP-2 (gelatinase A) (Roher et al. 1994) and MMP-9 (gelatinase B) (Backstrom et al. 1996), which can also degrade the fibrillar form of Ab, as well as compact plaques (Yan et al. 2006).”
BackgroundAmyloid β Oligomers Disrupt Blood–CSF Barrier Integrity by Activating Matrix Metalloproteinases
Brkić, M. P., Balusu, S., Wonterghem, E. V., Gorlé, N., Benilova, I., Kremer, A., van Hove, I., Moons, L., de Strooper, B., Kanazir, S., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0006-15.2015 · Cited by 167 · see citing works
“For example, CSF and brain MMP levels are higher in Alzheimer’s disease patients than in age-matched controls and MMPs have been implicated in degradation of A (Guo et al., 2006; Yan et al., 2006; Yin et al., 2006; Hanzel et al., 2014; Kauwe et al., 2014; Mroczko et al., 2014).”
BackgroundBehl, T., Kaur, G., Sehgal, A., Bhardwaj, S., Singh, S., Buhaș, C. L., Pusta, C. T. J., Uivaroșan, D., Munteanu, M. A., & BUNGAU, S. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031413 · Cited by 192 · see citing works
Activation of the CB2 receptor system reverses amyloid-induced memory deficiency
Wu, J., Bie, B., Yang, H., Xu, J. J., Brown, D. L., & Naguib, M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.06.011 · Cited by 174 · see citing works
Self-citationMizuno, T., Doi, Y., Mizoguchi, H., Jin, S., Noda, M., Sonobe, Y., Takeuchi, H., & Suzumura, A. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.06.011 · Cited by 159 · see citing works
Vesce, S., Rossi, D., Brambilla, L., & Volterra, A. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(07)82003-4 · Cited by 159 · see citing works
Loss of Neprilysin Function Promotes Amyloid Plaque Formation and Causes Cerebral Amyloid Angiopathy
Farris, W., Schütz, S. G., Cirrito, J. R., Shankar, G. M., Sun, X., George, A., Leissring, M. A., Walsh, D. M., Qiu, W. Q., Holtzman, D. M., et al. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.070105 · Cited by 155 · see citing works
“NEP can degrade soluble A but not aggregated fibrils of the peptide.(42) Most of the GuHCl-extracted brain A measured in the 13-month-old animals probably existed as protease-resistant extracellular deposits (ie, plaques and CAA) in vivo.”
BackgroundSelf-citationTargeting amyloid clearance in Alzheimer's disease as a therapeutic strategy
Nalivaeva, N. N., & Turner, A. J. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14593 · Cited by 172 · see citing works
Microglial degeneration in the aging brain - bad news for neurons?
Streit, W. (2008) · Frontiers in Bioscience · doi:10.2741/2937 · Cited by 150 · see citing works
“On the other hand, recent studies show that neprilysin cannot degrade the fibrillar beta-amyloid commonly found in dense plaques (182) or especially neurotoxic oligomeric beta-amyloid (183).”
CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia
Parajuli, B., Horiuchi, H., Mizuno, T., Takeuchi, H., & Suzumura, A. (2015) · Glia · doi:10.1002/glia.22892 · Cited by 160 · see citing works
“Neuronal survival was assessed by MAP-2–specific immunofluorescence staining, as described previously (Mizuno et al., 2008, 2011; Yan et al., 2006).”
MethodAlzheimer Disease and Its Growing Epidemic
Hickman, R. A., Faustin, A., & Wısnıewskı, T. (2016) · Neurologic Clinics · doi:10.1016/j.ncl.2016.06.009 · Cited by 156 · see citing works
“Neprilysin, metalloproteinase-9, and several other factors that are released by healthy microglia digest Ab.98 There is a heightened neuroinflammatory response following TBI that persists, and the activation of microglia most likely releases factors that assist in the digestion of Ab.”
BackgroundIncreased Matrix Metalloproteinase-9 Activity in Mild Cognitive Impairment
Bruno, M., Mufson, E., Wuu, J., & Cuello, A. (2009) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e3181c22569 · Cited by 143 · see citing works
“with ApoE ?4 allele (%) 1 (12) 2 (18) 4 (40) 7 (24) p = 0.”
The Neurovascular Unit in Health and Disease
Lo, E. H., & Rosenberg, G. A. (2008) · Stroke · doi:10.1161/strokeaha.108.534404 · Cited by 135 · see citing works
Doi, Y., Mizuno, T., Maki, Y., Jin, S., Mizoguchi, H., Ikeyama, M., Doi, M., Michikawa, M., Takeuchi, H., & Suzumura, A. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.090418 · Cited by 135 · see citing works
“MMP-9, a protease that degrades A , is expressed at higher levels in the brains of AD patients and may play an important role in amyloid clearance by degrading both oA and fA .(10) MMP-9 expression is increased by serum amyloid A through formyl peptide receptor-like-1.”
BackgroundGlial cells in Alzheimer’s disease: From neuropathological changes to therapeutic implications
Uddin, M. S., & Lim, L. W. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101622 · Cited by 149 · see citing works
Critical review: involvement of endoplasmic reticulum stress in the aetiology of Alzheimer's disease
Hashimoto, S., & Saido, T. C. (2018) · Open Biology · doi:10.1098/rsob.180024 · Cited by 129 · see citing works
Ma, T., Gong, K., Ao, Q., Yan, Y., Song, B., Huang, H.-Y., Zhang, X.-F., & Gong, Y.-D. (2013) · Cell Transplantation · doi:10.3727/096368913x672181 · Cited by 128 · see citing works
Microglial complement receptor 3 regulates brain Aβ levels through secreted proteolytic activity
Czirr, E., Castello, N. A., Mosher, K. I., Castellano, J. M., Hinkson, I. V., Lucin, K. M., Baeza-Raja, B., Ryu, J. K., Li, L., Farina, S. N., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162011 · Cited by 126 · see citing works
“EDTA is a strong inhibitor of metalloproteinases, and matrix metalloproteinase 2 (MMP2) and MMP9 have previously been implicated as major Aβ-degrading enzymes (Yan et al., 2006; Hernandez-Guillamon et al., 2010).”
BackgroundSelf-citationHemming, M. L., Selkoe, D., & Farris, W. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.01.004 · Cited by 126 · see citing works
Kauwe, J. S. K., Bailey, M. H., Ridge, P. G., Perry, R., Wadsworth, M. E., Hoyt, K. L., Staley, L. A., Karch, C. M., Harari, O., Cruchaga, C., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004758 · Cited by 125 · see citing works
“MMP9 can degrade fibrillar Ab in vitro and plaques in hippocampal slice cultures [52,56,57].”
Self-citationUltrastructural evidence of microglial heterogeneity in Alzheimer’s disease amyloid pathology
El Hajj, H., Savage, J. C., Bisht, K., Parent, M., Vallières, L., Rivest, S., & Tremblay, M.-È. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1473-9 · Cited by 119 · see citing works
“Additionally, microglia were involved in extracellular degradation of Aβ both in vitro and in vivo [29, 30].”
BackgroundDiversity of astroglial responses across human neurodegenerative disorders and brain aging
Ferrer, I. (2017) · Brain Pathology · doi:10.1111/bpa.12538 · Cited by 123 · see citing works
“The mechanisms used by reactive astrocytes to degrade b-amyloid are multiple and complementary, including activation of metalloproteinases (480, 485) and lysosomal degradation (30, 249, 477).”
BackgroundKurapati, K. R. V., Atluri, V., Samikkannu, T., & Nair, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077624 · Cited by 117 · see citing works
“angiotensin-converting enzyme, plasminogen activator and matrix metalloproteinase-9 [58-62].”
BackgroundHuman neural stem cell transplantation improves cognition in a murine model of Alzheimer’s disease
McGinley, L. M., Kashlan, O. N., Bruno, E. S., Chen, K. S., Hayes, J., Kashlan, S. R., Raykin, J., Johe, K., Murphy, G. G., & Feldman, E. (2018) · Scientific Reports · doi:10.1038/s41598-018-33017-6 · Cited by 115 · see citing works
Cerebral amyloid angiopathy: pathogenetic mechanisms and link to dense amyloid plaques
Kumar‐Singh, S. (2008) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00380.x · Cited by 94 · see citing works
“Other molecules with similar function and of potential therapeutic relevance are AchE (Rees et al. 2003) and ganglioside GM1 (Yanagisawa et al. 1995).”
BackgroundStargardt, A., Swaab, D. F., & Bossers, K. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.014 · Cited by 109 · see citing works
“In addition to NEP, the matrix metalloproteinase-9 (MMP-9) has received considerable attention for its Ab degrading capacity (Backstrom et al., 1996; Merlo and Sortino, 2012; Yan et al., 2006) and its ability to elevate secreted APPa levels, the product of the nonamyloidogenic pathway of APP processing (Fragkouli et a…”
Sequential Amyloid-β Degradation by the Matrix Metalloproteases MMP-2 and MMP-9*
Hernández-Guillamon, M., Mawhirt, S., Blais, S., Montaner, J., Neubert, T., Rostagno, A., & Ghiso, J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610931 · Cited by 110 · see citing works
“In contrast, MMP-9 has been reported to partially degrade preformed A fibrils (9), generating few identifiable truncated fragments (A (1–20) and A (1–30)) that do not match the sequence of events described in our studies employing soluble A 40 and A 42 homologues.”
BackgroundMatrix Metalloproteinases and Their Multiple Roles in Alzheimer's Disease
Wang, X.-X., Tan, M., Yu, J.-T., & Tan, L. (2014) · BioMed Research International · doi:10.1155/2014/908636 · Cited by 110 · see citing works
“MMP-9 induces Aβ, degrades Aβ and compact plaques, and is released, along with proNGF, in an activity dependent manner [24].”
Cathepsin B Degrades Amyloid-β in Mice Expressing Wild-type Human Amyloid Precursor Protein*
Wang, C., Sun, B.-G., Zhou, Y.-G., Grubb, A., & Gan, L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.371641 · Cited by 109 · see citing works
Li, X., & Buxbaum, J. N. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-79 · Cited by 100 · see citing works
“Ab can be degraded by a number of proteases including angiotensin converting enzyme (ACE) [79,80], Cathepsin B [81], endothelin converting enzymes (ECE) [82], glutamate carboxypeptidase II [83], matrix metalloproteinases (MMP-2/gelatinase A [84], MMP-9/gelatinase B [85,86]), plasmin [87,88], neprilysin”
BackgroundLiu, R.-M., van Groen, T., Katre, A., Cao, D.-F., Kadisha, I., Ballinger, C., Wang, L., Carroll, S. L., & Li, L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.06.003 · Cited by 108 · see citing works
Stomrud, E., Björkqvist, M., Janciauskiene, S. M., Minthon, L., & Hansson, O. (2010) · Alzheimer s Research & Therapy · doi:10.1186/alzrt44 · Cited by 105 · see citing works
“Moreover, MMP-3 and MMP-9 can cleave and degrade Ab fibrils [8,13].”
BackgroundRecent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer's disease.
Madav, Y., Wairkar, S., & Prabhakar, B. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.01.004 · Cited by 102 · see citing works
Matrix Metalloproteinases, New Insights into the Understanding of Neurodegenerative Disorders
Kim, Y.-S., & Joh, T. H. (2012) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2012.20.2.133 · Cited by 103 · see citing works
“MMPs may directly de-grade Aβ resulting in reduction in Aβ deposit (Yan et al., 2006; Miners et al., 2008).”
BackgroundLu, X.-Y., Huang, S., Chen, Q.-B., Zhang, D.-P., Li, W., Ao, R., Leung, F. C.-Y., Zhang, Z.-M., Huang, J.-S., Tang, Y., et al. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2315106 · Cited by 98 · see citing works
Hernández‐Guillamón, M., Martínez-Sáez, E. A., Delgado, P., Domingues‐Montanari, S., Boada, C., Peñalba, A., Boada, M., Pagola, J., Maisterra, O., Rodríguez‐Luna, D., et al. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00512.x · Cited by 96 · see citing works
“Despite the ability to degrade a range of protein substrates, as certain components of the basal lamina, MMP-2 and MMP-9 can proteolyse different Ab peptides in vitro (4, 7, 10, 20, 32).”
BackgroundMolecular imaging of neuroinflammation in Alzheimer's disease and mild cognitive impairment
Knezevic, D., & Mizrahi, R. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.05.007 · Cited by 97 · see citing works
“It has been proposed that microglia attempt to clear the brain of amyloid through the phagocytosis of Aβ and secretion of proteolytic enzymes that degrade Aβ (Leissring et al., 2003; Yan et al., 2006).”
Multiple functions of insulin-degrading enzyme: a metabolic crosslight?
Tundo, G. R., Sbardella, D., Ciaccio, C., Grasso, G., Gioia, M., Coletta, A., Polticelli, F., Pierro, D. D., Milardi, D., Endert, P. V., et al. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1337707 · Cited by 101 · see citing works
“Cytosolic enzymes capable of degrading nontoxic oligomers likely do not exist and in the extracellular space only the MMP-9 was described to be able to partially degrade amyloid plaques (Yan et al. 2006).”
BackgroundMulder, S., Veerhuis, R., Blankenstein, M., & Nielsen, H. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.11.001 · Cited by 95 · see citing works
Matrix Metalloproteinases as New Targets in Alzheimer’s Disease: Opportunities and Challenges
Zipfel, P., Rochais, C., Baranger, K., Rivera, S., & Dallemagne, P. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00352 · Cited by 94 · see citing works
Matrix Metalloproteinase in Blood-Brain Barrier Breakdown in Dementia
Weekman, E. M., & Wilcock, D. M. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150759 · Cited by 103 · see citing works
Rivera, S., García‐González, L., Khrestchatisky, M., & Baranger, K. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03178-2 · Cited by 112 · see citing works
Liao, M.-C., & Nostrand, W. V. V. (2010) · Biochemistry · doi:10.1021/bi901994d · Cited by 91 · see citing works
“MMP9, like MT1-MMP, cleaves between residues Ala30-Ile31 (37).”
BackgroundMethodInfluentialA new face for old antibiotics: tetracyclines in treatment of amyloidoses.
Stoilova, T., Colombo, L., Forloni, G., Tagliavini, F., & Salmona, M. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400161p · Cited by 89 · see citing works
Mizoguchi, H., Takuma, K., Fukuzaki, E., Ibi, D., Someya, E., Akazawa, K., Alkam, T., Tsunekawa, H., Mouri, A., Noda, Y., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.154724 · Cited by 87 · see citing works
“Notably, MMP-9 was reported to cleave insoluble A in vitro (Yan et al., 2006).”
BackgroundInfluentialECM 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 · see citing works
“, 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.”
InfluentialMatrix 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 83 · see citing works
“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).”
BackgroundHollow core of Alzheimer’s Aβ42 amyloid observed by cryoEM is relevant at physiological pH
Miller, Y., Ma, B., Tsai, C.-J., & Nussinov, R. (2010) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1004704107 · Cited by 84 · see citing works
“(2009) Comparison of Alzheimer Abeta(1-40) and Abeta(1-42)”
BackgroundInfluentialMMP-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 89 · see citing works
“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).”
BackgroundAmyloid-β and Astrocytes Interplay in Amyloid-β Related Disorders
Batarseh, Y. S., Duong, Q.-V., Mousa, Y. M., Rihani, S. B. A., Elfakhri, K. H., & Kaddoumi, A. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030338 · Cited by 80 · see citing works
“Beside transport proteins, astrocytes mediate the clearance of Aβ directly by endocomal-lysosomal pathways subjecting Aβ to degradation by a variety of degrading enzymes such as insulin-degrading enzyme (IDE) and neprilysin (NEP) that are only effective on the degradation of Aβ monomers [52,53], while matrix metallopr…”
BackgroundMatrix Metalloproteinases in Alzheimer’s Disease and Concurrent Cerebral Microbleeds
Duits, F., Hernández-Guillamon, M., Montaner, J., Goos, J. D. C., Montañola, A., Wattjes, M., Barkhof, F., Scheltens, P., Teunissen, C., & van der Flier, W. M. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-143186 · Cited by 82 · see citing works
“Post-hoc tests showed higher CSF MMP10 levels in AD patients compared to controls (median [IQR] 25 [16–35] versus 13 [10–20] pg/mL, p= 0.”
InfluentialProfiles of matrix metalloproteinases and their inhibitors in plasma of patients with dementia
Lorenzl, S., Büerger, K., Hampel, H. J., & Beal, M. F. (2007) · International Psychogeriatrics · doi:10.1017/s1041610207005790 · Cited by 96 · see citing works
Tzeng, T.-T., Chen, C.-C., Chen, C.-C., Tsay, H., Lee, L.-Y., Chen, W.-P., Shen, C.-C., & Shiao, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020598 · Cited by 81 · see citing works
“It is well established that plaques are visible in 6 month old APP/PS1 mice [23].”
BackgroundMethodZhang, K., Li, T. X., Liu, L., Feng, Y., Dong, Y.-B., Li, B., Shang, D., Fang, W., Cao, Y., & Chen, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072744 · Cited by 84 · see citing works
“Aβ deposition and limit AD process [12,13], thus performing a neuroprotective role in AD.”
BackgroundRestored degradation of the Alzheimer’s amyloid‐β peptide by targeting amyloid formation
Crouch, P., Tew, D., Du, T., Nguyen, D. N., Caragounis, A., Filiz, G., Blake, R., Trounce, I. A., Soon, C. P., Laughton, K. M., et al. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05870.x · Cited by 81 · see citing works
“Consistent with previous reports (Roher et al. 1994; Backstrom et al. 1996; Yan et al. 2006) surface enhanced laser desorption ionisation time of flight mass spectrometry analysis showed MMP-mediated generation of an Ab fragment with a mass equal to Ab1–34 (Ab34), indicating cleavage between Ab residues leu34 and met3…”
ResultCrouch, P., White, A., & Bush, A. I. (2007) · The FEBS Journal · doi:10.1111/j.1742-4658.2007.05918.x · Cited by 81 · see citing works
Nitric Oxide Synthase-2-Derived Nitric Oxide Drives Multiple Pathways of Breast Cancer Progression
Basudhar, D., Somasundaram, V., de Oliveira, G. A., Kesarwala, A., Heinecke, J. L., Cheng, R. Y. S., Glynn, S., Ambs, S., Wink, D., & Ridnour, L. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6813 · Cited by 80 · see citing works
“HIF-1a stabilization by NO activates a number of signaling pathways mediated by the promoter hypoxia response element (HRE) to confer survival and growth advantage, angiogenesis, wound repair, and tumor development (130, 163).”
BackgroundMatrix Metalloproteases as Influencers of the Cells’ Social Media
Young, D., Das, N. S., Anowai, A., & Dufour, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163847 · Cited by 77 · see citing works
Quan, Q.-K., Wang, J., Li, X., & Wang, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059155 · Cited by 77 · see citing works
“Ab is degraded by many proteases, including neprilysin [43,44], endothelin-converting enzyme [45,46], angiotensin-converting enzyme [47], plasminogen activator [48,49], and matrix metalloproteinase-9 [50].”
BackgroundNeuroprotective role of MMP-9 overexpression in the brain of Alzheimer's 5xFAD mice.
Fragkouli, A., Tsilibary, E. C., & Tzinia, A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.06.021 · Cited by 76 · see citing works
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 · see citing works
Son, S., Song, H., Byun, J., Park, K., Jang, H., Park, Y., & Mook-Jung, I. (2012) · Diabetes · doi:10.2337/db11-1735 · Cited by 74 · see citing works
Self-citationDisease-Modifying Therapies in Alzheimer???s Disease
ll, M. H., Berger, T., & Heneka, M. T. (2006) · Drugs · doi:10.2165/00003495-200666160-00004 · Cited by 94 · see citing works
Lacoste, B., Tong, X.-K., Lahjouji, K., Couture, R., & Hamel, E. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-57 · Cited by 73 · see citing works
“As MMP9 is involved in both BBB integrity and Aβ clearance [40-43], its protein levels were also measured.”
Trikha, S., & Jeremic, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.240762 · Cited by 73 · see citing works
- 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
- Health Sciences › Medicine › Physiology › 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
