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Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-β peptide (1–40).
Open accessAbstract
We reported earlier that the levels of Ca 2+ -dependent metalloproteinases are increased in Alzheimer’s disease (AD) specimens, relative to control specimens. Here we show that these enzymes are forms of the matrix metalloproteinase MMP-9 (EC 3.4.24.35 ) and are expressed in the human hippocampus. Affinity-purified antibodies to MMP-9 labeled pyramidal neurons, but not granular neurons or glial cells. MMP-9 mRNA is expressed in pyramidal neurons, as determined with digoxigenin-labeled MMP-9 riboprobes, and the presence of this mRNA is confirmed with reverse transcriptase PCR. The cellular distribution of MMP-9 is altered in AD because 76% of the total 100 kDa enzyme activity is found in the soluble fraction of control specimens, whereas only 51% is detectable in the same fraction from AD specimens. The accumulated 100 kDa enzyme from AD brain is latent and can be converted to an active form with aminophenylmercuric acetate. MMP-9 also is detected in close proximity to extracellular amyloid plaques. Because a major constituent of plaques is the 4 kDa β-amyloid peptide, synthetic Aβ 1–40 was incubated with activated MMP-9. The enzyme cleaves the peptide at several sites, predominantly at Leu 34 -Met 35 within the membrane-spanning domain. These results establish that neurons have the capacity to synthesize MMP-9, which, on activation, may degrade extracellular substrates such as β-amyloid. Because the latent form of MMP-9 accumulates in AD brain, it is hypothesized that the lack of enzyme activation contributes to the accumulation of insoluble β-amyloid peptides in plaques.
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“Increasing in vitro evidence indicates that some MMPs may play an important role in degrading soluble Ab (sAb), such as secreted MMP-2 and MMP-9 that generate C-terminally truncated Ab fragments and membrane-type MMP-14 that degrades both soluble and fibrillary Ab (29)(30)(31)(32).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [29]
Experimental — accuracy not yet measuredIn the citing paper
“In parallel, a number of these CNS diseases exhibit dysregulated expression of enzymes necessary for PNN cleavage and reorganization (Backstrom et al., 1996; Lorenzl et al., 2003; Rybakowski et al., 2009; Kim et al., 2009; Zhang et al., 2011; Yamamori et al., 2013; Liu et al., 2014; Rankin-Gee et al., 2015; Lepeta et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
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“plasma levels of MMP-9 are elevated in AD patients (Backstrom et al., 1996; Lorenzl et al., 2003).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
In the citing paper
“MMP-9 is capable of cleaving Aβ in vitro (Backstrom et al., 1996)”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
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“In extracellular space, some polypeptides can also be cleaved by MMP-9 [39].”
BackgroundMatrix metalloproteinases and their multiple roles in neurodegenerative diseases
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“…2006;Wang et al., 2012), aminopeptidase (Sevalle et al., 2009; Dhanavade and Sonawane, 2014), gelatinase A (Yamada et al., 1995b; Jalkute et al., 2015), matrix metalloendopeptidase-9 (Backstrom et al., 1996), coagulation factor Xia (Saporito-Irwin and Van Nostrand, 1995), antibody light chain c23.”
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“…GK diabetic rat, a compelling model of type 2 diabetes mellitus (Fakhrai-Rad et al., 2000).in vitro conditions include matrix metalloproteinase-9 (Backstrom et al., 1996) and cathepsin D (McDermott In separate experiments, an apparently distinct linkage region has been localized to…”
BackgroundZinc Metabolism in the Brain: Relevance to Human Neurodegenerative Disorders
Cuajungco, M. P., & Lees, G. J. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0163 · Cited by 544
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“Other proteases that have been reported to digest synthetic A under in vitro conditions include matrix metalloproteinase-9 (Backstrom et al., 1996) and cathepsin D (McDermott and Gibson, 1996).”
BackgroundMultiple roles for MMPs and TIMPs in cerebral ischemia
Cunningham, L. A., Wetzel, M. K., & Rosenberg, G. A. (2005) · Glia · doi:10.1002/glia.20169 · Cited by 412
“…et al., 2003), microglia (Mentlein et al., 1998; Cross and Woodroofe, 1999; Mayer et al., 2001), oligodendrocytes (Oh et al., 1999), and neurons (Backstrom et al., 1996; Vecil et al., 2000; HayashitaKinoh et al., 2001; Conant et al., 2002; Wetzel et al., 2003; Conant et al., 2004; Wetzel et…”
BackgroundSzklarczyk, A., Lapinska, J., Rylski, M., McKay, R. D. G., & Kaczmarek, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00920.2002 · Cited by 392
MMP ‐9 in translation: from molecule to brain physiology, pathology, and therapy
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“Backstrom et al. (1996) studied postmortem brain tissue from AD patients and reported that MMP-9 was localized to neurons in the hippocampus and capable of degrading Ab.”
BackgroundCauwe, B., den Steen, P. E. V., & Opdenakker, G. (2007) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230701340019 · Cited by 389
“Interestingly, the human hippocampus of Alzheimer’s disease patients shows increased levels of pro-MMP-9 near the amyloid plaques (Backstrom et al., 1996) and the same increase was reported in amyloidpositive beagle brains (Lim et al., 1997).”
BackgroundInfluentialMiners, J. S., Baig, S., Palmer, J. C., Palmer, L. E., Kehoe, P. G., & Love, S. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00132.x · Cited by 393
“35) all have Ab-degrading activity in vitro (10).”
Matrix Metalloproteinase-9 Degrades Amyloid-β Fibrils in Vitro and Compact Plaques in Situ
Yan, P., Hu, X., Song, H., Yin, K., Bateman, R. J., Cirrito, J. R., Xiao, Q., Hsu, F. F., Turk, J. W., Xu, J., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602440200 · Cited by 380
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Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme*
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Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-β Peptide Catabolism
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“Incubation of A with ACM resulted in a significant decline in A levels and caused the appearance of several A fragments, including 1–20, 1–30, and 1–34, that are characteristic of MMP cleavage (Roher et al., 1994; Backstrom et al., 1996).”
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“Enzyme Name Substrate Levels/Activity in AD Brain vs. Control Metal - Binding References Neprilysin Aβ, Bradykinin, Substance P, Angiotensin-I, Angiotensin-II, Endothelin-1, Kinins, Adrenomedullin, Opioid peptides, enkephalin, gastrin Increased Reduced Zinc [150, 149] Endothelin-converting enzymes (ECE) Aβ, Endothelin…”
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White, A. R., Du, T., Laughton, K. M., Volitakis, I., Sharples, R. A., Xilinas, M. E., Hoke, D. E., Holsinger, R. M. D., Evin, G., Cherny, R. A., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602487200 · Cited by 284
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BackgroundClearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes
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BackgroundAstrocytic LRP1 Mediates Brain Aβ Clearance and Impacts Amyloid Deposition
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“metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-β peptide (1-40).”
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“NEP is pivotal in the hydrolysis of neuropeptides at the synapse, including substance P and the enkephalins (Turner and Tanzawa 1997; Turner et al. 2001). symbol / between residues show the major cleavage sites determined for the following metallopeptidases: A, angiotensin-converting en- zyme; N, NEP (Howell et al. 19…”
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“…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).”
BackgroundCorona, C., Masciopinto, F., Silvestri, E., Viscovo, A. D., Lattanzio, R., Sorda, R. L., Ciavardelli, D., Goglia, F., Piantelli, M., Canzoniero, L. M. T., et al. (2010) · Cell Death and Disease · doi:10.1038/cddis.2010.73 · Cited by 189
β ‐Amyloid Degradation and Alzheimer′s Disease
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“These include neprilysin (NEP) [14– 16], endothelin-converting enzyme (ECE)-1 [17], insulindegrading enzyme (IDE) [18–20], angiotensin-converting enzyme (ACE) [21], uPA/tPA-plasmin system [22, 23], cathepsin D [24, 25], gelatinase A [26], gelatinase B [27], matrix metalloendopeptidase-9 [28], coagulation factor XIa [2…”
BackgroundThe Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00270 · Cited by 170
“Interestingly, some studies suggest that MMP-9 may be a key molecular target in treating AD, as MMP-9 is capable of cleaving Aβ in vitro (Backstrom et al., 1996), and plasma levels of MMP-9 are elevated in AD patients (Backstrom et al., 1996; Lorenzl et al., 2003).”
BackgroundWalker, D. G., Link, J., Lue, L., Dalsing-Hernandez, J. E., & Boyes, B. E. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0705377 · Cited by 183
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Gene expression correlates of neurofibrillary tangles in Alzheimer's disease
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“Further, matrix metalloproteinase 9, which is a target of TIMP inhibition, has been reported to be upregulated in plasma of AD patients [23] and has been implicated in the degradation of toxic β-amyloid species [2].”
BackgroundRegulation of Matrix Metalloproteinase Gene Expression
Fini, M. E., Cook, J. R., Mohan, R., & Brinckerhoff, C. (1998) · Elsevier eBooks · doi:10.1016/b978-012545090-4/50013-6 · Cited by 177
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Sallés, F. J., & Strickland, S. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02125.2002 · Cited by 166
“…synaptic plasticity Extracellular proteases are expressed by neurons in the CNS (Sappino et al., 1993; Chen et al., 1995; Nishibori et al., 1995; Backstrom et al., 1996; Gschwend et al., 1997; Scarisbrick et al., 2001), and their function can vary from potentiating synaptic transmission…”
BackgroundLorenzl, S., Albers, D. S., LeWitt, P. A., Chirichigno, J. W., Hilgenberg, S. L., Cudkowicz, M., & Beal, M. F. (2003) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(02)00398-2 · Cited by 165
“One family of proteases, namely matrix metalloproteinases (MMPs), can remodel the extracellular matrix and additionally digest pathologically accumulated extracellular proteins like amyloid [2].”
BackgroundIncreased Matrix Metalloproteinase 9 Activity in Mild Cognitive Impairment
Bruno, M. A., Mufson, E. J., Wuu, J., & Cuello, A. C. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181c22569 · Cited by 163
“Matrix metalloproteinase 9 induces amyloid-A peptides (AA) (14, 15), degrades amyloid A (16, 17) and compact plaques (18), and is released, along with proNGF, in an activitydependent manner (10).”
MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth.
Kalafatovic, D., Nobis, M., Son, J., Anderson, K., & Ulijn, R. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.04.039 · Cited by 140
Miners, J. S., Helmond, Z. V., Chalmers, K. A., Wilcock, G. K., Love, S., & Kehoe, P. G. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240463.87886.9a · Cited by 156
Wright, J. W., & Harding, J. W. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.03.003 · Cited by 158
Rivera, S., Ogier, C., Jourquin, J., Timsit, S., Szklarczyk, A. W., Miller, K., Gearing, A. J. H., Kaczmarek, L., & Khrestchatisky, M. (2002) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01838.x · Cited by 128
Alzheimer’s disease: How metal ions define β-amyloid function
Kepp, K. P. (2017) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2017.05.007 · Cited by 154
Lee, K., Kim, J., Seo, J., Kim, T., Im, J., Baek, I., Kim, K., Lee, J., & Han, P. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05769.x · Cited by 149
DeLeve, L. D., Wang, X., Tsai, J., Kanel, G. C., Strasberg, S. M., & Tökés, Z. A. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01056-4 · Cited by 144
Self-citationSequential Amyloid-β Degradation by the Matrix Metalloproteases MMP-2 and MMP-9
Hernandez-Guillamon, M., Mawhirt, S., Blais, S., Montaner, J., Neubert, T. A., Rostagno, A., & Ghiso, J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610931 · Cited by 137
The TIMPs tango with MMPs and more in the central nervous system
Crocker, S. J., Pagenstecher, A., & Campbell, I. L. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10836 · Cited by 137
“…proteolysis regulated by TIMPs may participate in other pathological changes in AD, including neurite outgrowth though the mobilization of growth factors from the ECM (McFarlane, 2003) and formation of amyloid plaques and fibrillary tangles in AD (Peress et al., 1995; Backstrom et al., 1996).”
BackgroundKauwe, 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
“MMP9 can degrade fibrillar Ab in vitro and plaques in hippocampal slice cultures [52,56,57].”
Baranger, K., Marchalant, Y., Bonnet, A. E., Crouzin, N., Carrete, A., Paumier, J.-M., Py, N. A., Bernard, A., Bauer, C., Charrat, E., et al. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1992-1 · Cited by 133
Ward, N. L., & Lamanna, J. C. (2004) · Neurological Research · doi:10.1179/016164104x3798 · Cited by 122
Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin
Tsirka, S. E., Bugge, T. H., Degen, J. L., & Strickland, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9779 · Cited by 125
Alzheimer’s disease due to loss of function: A new synthesis of the available data
Kepp, K. P. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.06.004 · Cited by 123
In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders
Pantazopoulos, H., & Berretta, S. (2015) · Neural Plasticity · doi:10.1155/2016/9847696 · Cited by 128
Loss of perineuronal net N-acetylgalactosamine in Alzheimer’s disease
Baig, S., Wilcock, G. K., & Love, S. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1060-2 · Cited by 112
“Other possible sources of PN-degrading proteases include astrocytes [14, 22, 23, 50, 53] and the neurons themselves [ 3 , 50, 53].”
BackgroundKoronyo‐Hamaoui, M., Ko, M. K., Koronyo, Y., Azoulay, D., Seksenyan, A., Kunis, G., Pham, M. D., Bakhsheshian, J., Rogeri, P. S., Black, K. L., et al. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06402.x · Cited by 116
Rivera, S., García-González, L., Khrestchatisky, M., & Baranger, K. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03178-2 · Cited by 111
Recent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer's disease
Madav, Y., Wairkar, S., & Prabhakar, B. R. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.01.004 · Cited by 122
Horstmann, S., Budig, L., Gardner, H., Koziol, J. A., Deuschle, M., Schilling, C., & Wagner, S. (2010) · International Psychogeriatrics · doi:10.1017/s1041610210000827 · Cited by 111
“Backstrom et al. argued that the inflammatory protein α1antichymotrypsin, which accumulates in amyloid plaques and which is a known inhibitor of serine proteinases, may prevent activation of MMP-9 and thereby contribute to reduced cleavage of amyloid β (Backstrom et al., 1996).”
BackgroundInfluentialBi, X., Gall, C. M., Zhou, J., & Lynch, G. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00132-x · Cited by 92
Nagai, T., Yamada, K., Yoshimura, M., Ishikawa, K., Miyamoto, Y., Hashimoto, K., Noda, Y., Nitta, A., & Nabeshima, T. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306587101 · Cited by 111
Kolb, S., Lahrtz, F., Paul, R. H., Leppert, D., Nadal, D., Pfister, H., & Fontana, A. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00247-6 · Cited by 110
Stargardt, A., Swaab, D. F., & Bossers, K. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.08.014 · Cited by 109
“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…”
Zhang, J. W., Deb, S., & Gottschall, P. E. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00347.x · Cited by 109
“Because latent forms of MMP-9 accumulate in the brain tissue of Alzheimer’s patients, the lack of enzyme activation has been suggested to contribute to the accumulation of insolubleβ-amyloid peptides in plaques (Backstrom et al., 1996).”
BackgroundSekine‐Aizawa, Y., Hama, E., Watanabe, K., Tsubuki, S., Kanai‐Azuma, M., Kanai, Y., Arai, H., Aizawa, H., Iwata, N., & Saido, T. C. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01462.x · Cited by 97
“This possibility follows from studies showing that MMP-2 and MMP-9 proteolyse synthetic Ab peptides (Miyazaki et al., 1993; Backstrom et al., 1996).”
BackgroundStomrud, E., Björkqvist, M., Janciauskiene, S. M., Minthon, L., & Hansson, O. (2010) · Alzheimer s Research & Therapy · doi:10.1186/alzrt44 · Cited by 107
“In light of these possible AD protecting effects of MMP-9, it has been suggested that the increased MMP-9 levels observed in AD might be of the inactive form [2,8,12].”
BackgroundResultInfluentialMorita‐Fujimura, Y., Fujimura, M., Gasche, Y. G., Copin, J., & Chan, P. H. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200001000-00017 · Cited by 105
Mohan, R., Rinehart, W. B., Bargagna‐Mohan, P., & Fini, M. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.25903 · Cited by 99
Imperlini, E., Gnecchi, M., Rognoni, P., Sabidó, E., Ciuffreda, M. C., Palladini, G. O., Espadas, G., Mancuso, F. M., Bozzola, M., Malpasso, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15424-3 · Cited by 97
Pihlaja, R., Koistinaho, J., Kauppinen, R., Sandholm, J., Tanila, H., & Koistinaho, M. (2011) · Glia · doi:10.1002/glia.21212 · Cited by 96
“Also insulin-degrading enzyme (Kurochin and Goto, 1994; Qiu et al., 1998), plasmin (Tucker et al., 2000), matrix metalloproteases (MMP-2 and -9) (Backstrom et al., 1996; Roher et al., 1994), angiotensin-converting enzyme (ACE) (Hu et al., 2001), and cathepsin D (McDermott and Gibson, 1996) have…”
BackgroundMatrix Metalloproteinases in Non-Neoplastic Disorders
Tokito, A., & Jougasaki, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071178 · Cited by 98
“MMP-9 has also been indicated to exert a neuroprotective effect via Aβ clearance, reducing the aggregation of the peptide [140,141].”
BackgroundProfiles 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
“MMP-9 is localized to neurons of the hippocampus and is capable of degrading Aβ (Backstrom et al. 1996).”
BackgroundHernández‐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 97
“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).”
BackgroundLiao, M.-C., & Van Nostrand, W. E. (2010) · Biochemistry · doi:10.1021/bi901994d · Cited by 92
“MMP9, like MT1-MMP, cleaves between residues Ala30-Ile31 (37).”
InfluentialMatrix 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
Ma, Z., Yang, J., Han, J., Gao, L., Liu, H., Lu, Z., Zhao, H., & Bie, X. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00922 · Cited by 94
The Aluminium-Amyloid Cascade Hypothesis and Alzheimer’s Disease
Exley, C. (2005) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/0-387-23226-5_11 · Cited by 93
Cattaud, V., Bezzina, C., Rey, C. C., Lejards, C., Dahan, L., & Verret, L. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.08.024 · Cited by 88
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
“It is interesting that MMP-9 is increased in the brains of AD patients (Backstrom et al., 1996).”
BackgroundInfluential
Metadata
- Authors
- Backstrom, J. R., Lim, G. P., Cullen, M. J., & Tökés, Z. A.
- Affiliations
- University of Southern California (US)
- ORCID
- Cullen, Michael J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-12-15
- Volume
- 16
- Issue
- 24
- Pages
- 7910-7919
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4296941341
- Cited by
- 331
- References
- 46
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 16 · 2020: 21 · 2019: 5 · 2018: 13 · 2017: 15 · 2016: 11 · 2015: 18 · 2014: 18 · 2013: 8 · 2012: 12
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Funders
- National Institute on Aging (R01-AG09681)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- MMP-9, Alzheimer's disease, Aβ40, hippocampal pyramidal neurons, MMP-9 mRNA expression, extracellular matrix metalloproteinases, transmembrane domain
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