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.
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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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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
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Sorted by citations
Items 301–334 of 334
Leite, J. P., & Gales, L. (2019) · doi:10.2210/pdb6ghx/pdb · Cited by 2
Multifaceted Role of Matrix Metalloproteases on Human Diseases
Roy, S., Pramanik, A., Chakraborti, T., & Chakraborti, S. (2017) · Springer eBooks · doi:10.1007/978-981-10-3162-5_2 · Cited by 2
“[32] demonstrated that MMP-9 can degrade Ab fibrils in vitro, as well as amyloid plaques in brain of aged APP/PS1 (double-transgenic AD mouse model expressing variants of amyloid precursor 2 Multifaceted Role of Matrix Metalloproteases on Human Diseases 25”
BackgroundKamboj, S., Harms, C., Wright, D., Nash, A., Klein-Seetharaman, J., & Sarkar, S. K. (2022) · doi:10.21203/rs.3.rs-1258797/v1 · Cited by 1
McNaugher, G. A., McColgan, L., Church, M., McClean, P. L., Gibson, D. S., Murray, E. K., Coyle, S., & McGilligan, V. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261456729 · Cited by 1
Gupta, A., Thirugnanam, K., Bice, Z., Lowman, A. K., Rarick, K. R., LaViolette, P. S., Pan, A., Franczak, M. B., & Ramchandran, R. (2026) · BMC Molecular and Cell Biology · doi:10.1186/s12860-026-00581-z · Cited by 1
“Astrocytes can also secrete enzymes Endothelin-converting enzyme-2 (ECE2) [10] or Matrix metalloprotease enzyme-9 (MMP-9) [11] that can preferentially degrade Aβ.”
A review of plant-derived products regulating amyloid beta-degrading enzymes in Alzheimer’s disease
Honaramouz, B., Imenshahidi, M., & Hosseinzadeh, H. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158053 · Cited by 1
Identification of Small Peptides in Human Cerebrospinal Fluid upon Amyloid-β Degradation
Mizuta, N., Yanagida, K., Kodama, T. S., Tomonaga, T., Takami, M., Ōyama, H., Kudo, T., Ikeda, M., Takeda, M., Tagami, S., et al. (2017) · Neurodegenerative Diseases · doi:10.1159/000453358 · Cited by 1
Wendt, G. (2014) · doi:10.22028/d291-23005 · Cited by 1
“Matrix Metalloproteinase 9 (MMP-9) Zn, Ca S M, O, F (Yan et al., 2006)”
BackgroundSleep, neuropeptides and proteases
Visniauskas, B., Julian, G., de Oliveira, R. D., Tufik, S., & Chagas, J. (2011) · Sleep Science · doi:10.1055/s-0046-1820327 · Cited by 1
Metaloproteinasas de matriz en las lesiones neurológicas: ¿una nueva diana terapéutica?
Vilalta, A., Sahuquillo, J., & Poca, M. (2010) · Revista de Neurología · doi:10.33588/rn.5102.2009643 · Cited by 1
Wang, Y., Xu, B., Zhou, J., Wang, J., Wang, G., & Cao, Y. (2021) · Acta Neurobiologiae Experimentalis · doi:10.21307/ane-2021-020 · Cited by 5
Price, B. R. (2019) · doi:10.13023/etd.2019.254 · Cited by 1
“suggests microglia serve neuroprotective roles in the AD brain [255, 272].”
BackgroundCatabolism and Anabolism of Amyloid-β
Hashimoto, S., Nilsson, P., & Saido, T. C. (2015) · Springer eBooks · doi:10.1007/978-4-431-55763-0_19 · Cited by 2
Proteases in the Nervous System
Cynis, H., Lichtenthaler, S. F., Wagner, L., & Demuth, H. (2013) · Springer eBooks · doi:10.1007/978-3-7091-0885-7_10 · Cited by 4
Bluhm, A., Grossmann, M., Minister, C., Schrempel, S., Joseph, M., Holzer, M., Sauter, C., Xiang, W., Feja, M., Schilling, S., et al. (2026) · Neurochemistry International · doi:10.1016/j.neuint.2026.106260
Sulatsky, M., Stepanenko, O., Stepanenko, O., Mikhailova, E. V., & Sulatskaya, A. I. (2026) · Protein Science · doi:10.1002/pro.70707
“Proteolytic enzyme-to-alpha-synuclein ratios of 1:25 and 1:50 were selected based on literature data for optimal catalytic activity (Stepanenko et al. 2024; Sulatsky et al. 2025a, 2025b; Yan et al. 2006).”
del Valle, M. L., & Arienzo, D. (2026) · Ibrain · doi:10.1002/ibra.70016
Liu, Y., Hsu, W.-L., Ma, Y.-L., Yin, C.-Y., & Lee, E. H. Y. (2026) · Journal of physiological investigation · doi:10.4103/ejpi.ejpi-d-25-00064
Haugen, F. O., & Silasi, G. (2025) · bioRxiv · doi:10.1101/2025.09.30.679680
“Moreover, APP/PSEN1 transgenic mice have shown to have increased MMP2 and MMP9 concentrations in astrocytes around amyloid plaques 28 .”
Epigenetic Shifts Reveal Alzheimer’s Origins after Sustained Picomolar Aβ ExposurePreprint
Paquola, A., Acquarone, E., Staniszewski, A., Teich, A. F., & Arancio, O. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.12.668749
“In addition, it has been found to be crucial for Aβ40 and Aβ42 degradation ( 69 ).”
Gardner, R. S., Kyle, M., Hughes, K., & Zhao, L.-R. (2024) · bioRxiv · doi:10.1101/2024.05.09.593359
“Levels of Mmp9 are increased in AD, and Mmp9 shows the ability to degrade Aβ plaques [138, 139].”
BackgroundImmune receptors and aging brain
Djurisic, M. R. (2024) · Bioscience Reports · doi:10.1042/bsr20222267 · Cited by 3
“Nevertheless, considering that neuroinflammation leads to increased levels of MHC-I expression [101,123], it is plausible that signaling through these receptors may be enhanced in the aging brain.”
BackgroundKim, H. Y., Kim, H. V., Jo, S., Lee, C. J., Choi, S. Y., Kim, D. J., & Kim, Y. S. (2015) · Nature Communications · doi:10.1038/ncomms9997 · Cited by 122
Abedi, V., Yeasin, M., & Zand, R. (2014) · International Conference on Computational Advances in Bio and Medical Sciences · doi:10.1109/iccabs.2014.6863929
Laurent, C. (2013) · theses.fr (ABES) · doi:10.70675/03ed9498z69bfz4543zb662z2c85c03cea04
“Plusieurs mécanismes moléculaires impliqués dans la clairance d’Aβ ont été mis en évidence tels que les récepteurs RAGE, CD36 et CD47 (Jones et al., 2013), ApoE et les récepteurs LDLr (Koistinaho et al., 2004), IDE (Leal et al., 2006) ou encore les métalloprotéases telles que MMP9 (Yan et al., 2006).”
Therapeutic potential of amyloid β-degrading enzymes in Alzheimer’s disease
Gan, L. (2007) · Future Neurology · doi:10.2217/14796708.2.2.133
Koch, B. M. E. (2019) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7716
“…enzymes 1 and 2 (ECE-1 and ECE-2), insulin degrading enzyme (IDE or isulysin), matrix metallopeptidases 2 and 9 (MMP2, MMP9) and serine protease tissue plasminogen activator (tPA) (Hernandez-Guillamon et al., 2010; Iwata et al., 2001; Melchor et al., 2003; Song and Hersh, 2005; Yan et al., 2006).”
BackgroundInvestigating Amyloid β toxicity in Drosophila melanogaster
Jonson, M. (2017) · Linköping studies in science and technology. Dissertations · doi:10.3384/diss.diva-138389
“Additionally, astrocytes have been observed to secrete matrix metalloproteinases (MMPs) that are important for the degradation of both monomeric Aβ and fibrillar Aβ deposits [174].”
BackgroundNeuroinflammation in Alzheimer's Disease and Vascular Cognitive Impairment
Weekman, E. M. (2017) · UKnowledge (University of Kentucky) · doi:10.13023/etd.2017.051
“(100) and even Aβ (106, 107), but they also have roles in axonal growth, synaptic”
BackgroundHettinger, J. C. (2017) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7jq10fn
“MMP-9, in fact, can degrade both soluble and fibrillar Aβ and is found in astrocytes surrounding 22 amyloid plaques in AD mouse models, potentially acting to reduce plaque load (Yan et al., 2006).”
BackgroundSerotonergic Signaling Pathways that Suppress Amyloid Beta in Mouse Models of AD
Fisher, J. R. (2014) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k74f1nr2
“These discoveries explain the mechanisms regulating amyloid beta reduction by serotonin activity and also offer a more selective therapy for Alzheimer's disease. metalloproteinase-9 (MMP9), are produced by glial cells to degrade Aβ (Yan et al., 2006; Yin et al., 2006; Hickman et al., 2008).”
BackgroundSpiller, K. J. (2014) · doi:10.7916/d8fn145w
“Not only can MMP-9 degrade soluble Aβ, it can also digest tightly aggregated Aβ fibrils (Yan et al., 2006).”
Background
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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