Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer’s disease?

Nalivaeva, Natalia N.; Beckett, Caroline; Belyaev, Nikolai D.; Turner, Anthony J.

doi:10.1111/j.1471-4159.2011.07510.x

Cited by 169

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Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer’s disease?

Nalivaeva, Natalia N., Beckett, Caroline, Belyaev, Nikolai D., Turner, Anthony J.·2012·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2011.07510.x

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Abstract

J. Neurochem. (2012) 120 (Suppl. 1), 167–185. The amyloid cascade hypothesis of Alzheimer’s disease envisages that the initial elevation of amyloid β‐peptide (Aβ) levels, especially of Aβ 1‐42, is the primary trigger for the neuronal cell death specific to onset of Alzheimer’s disease. There is now substantial evidence that brain amyloid levels are manipulable because of a dynamic equilibrium between their synthesis from the amyloid precursor protein and their removal by amyloid‐degrading enzymes (ADEs) providing a potential therapeutic strategy. Since the initial reports over a decade ago that two zinc metallopeptidases, insulin‐degrading enzyme and neprilysin (NEP), contributed to amyloid degradation in the brain, there is now an embarras de richesses in relation to this category of enzymes, which currently number almost 20. These now include serine and cysteine proteinases, as well as numerous zinc peptidases. The experimental validation for each of these enzymes, and which to target, varies enormously but up‐regulation of several of them individually in mouse models of Alzheimer’s disease has proved effective in amyloid and plaque clearance, as well as cognitive enhancement. The relative status of each of these enzymes will be critically evaluated. NEP and its homologues, as well as insulin‐degrading enzyme, remain as principal ADEs and recently discovered mechanisms of epigenetic regulation of NEP expression potentially open new avenues in manipulation of AD‐related genes, including ADEs.

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Physiologically relevant Aβ degradation is mainly attributed to four metalloproteinases: neprilysin, insulin degrading enzyme, endothelin converting enzyme and angiotensin converting enzyme.
“Physiologically relevant Aβ degradation has been mainly attributed to 4 metalloproteinases: neprilysin, insulin degrading enzyme, endothelin converting enzyme and angiotensin converting enzyme, the regulation and functions of which have been extensively reviewed elsewhere (De Strooper, 2010; Nalivaeva et al., 2012).”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Nalivaeva et al., 2012

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Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303
ADAM10 is the physiologically relevant, constitutive α‐secretase of the amyloid precursor protein in primary neurons
Kuhn, P., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., Kremmer, E., Roßner, S., & Lichtenthaler, S. F. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.167 · Cited by 621
RAGE (Yin) Versus LRP (Yang) Balance Regulates Alzheimer Amyloid β-Peptide Clearance Through Transport Across the Blood–Brain Barrier
Deane, R., Wu, Z., & Zlokovic, B. V. (2004) · Stroke · doi:10.1161/01.str.0000143452.85382.d1 · Cited by 392
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 · cited 1×
“…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).”
Background
Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-β peptide (1–40).
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 · cited 1×
“…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).”
Background
Physiological roles for amyloid β peptides
Pearson, H. A., & Peers, C. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.111203 · Cited by 286
Degradation of the Alzheimer Disease Amyloid β-Peptide by Metal-dependent Up-regulation of Metalloprotease Activity
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
Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease
Kehoe, P. G., Russ, C., McIlroy, S., Williams, H., Holmans, P., Holmes, C., Liolitsa, D., Vahidassr, D., Powell, J., McGleenon, B., et al. (1999) · Nature Genetics · doi:10.1038/5009 · Cited by 260
Cystatin C-Cathepsin B Axis Regulates Amyloid Beta Levels and Associated Neuronal Deficits in an Animal Model of Alzheimer's Disease
Sun, B., Zhou, Y., Halabisky, B., Lo, I., Cho, S.-H., Mueller-Steiner, S., Devidze, N., Wang, X., Grubb, A., & Gan, L. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.001 · Cited by 231
Large Meta-Analysis Establishes the ACE Insertion-Deletion Polymorphism as a Marker of Alzheimer's Disease
Lehmann, D. J., Cortina-Borja, M., Warden, D. R., Smith, A. D., Sleegers, K., Prince, J. A., van Duijn, C. M., & Kehoe, P. G. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi202 · Cited by 199
Regulation of Steady-state β-Amyloid Levels in the Brain by Neprilysin and Endothelin-converting Enzyme but Not Angiotensin-converting Enzyme
Eckman, E. A., Adams, S. K., Troendle, F. J., Stodola, B. A., Kahn, M. A., Fauq, A. H., Xiao, H. D., Bernstein, K. E., & Eckman, C. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605827200 · Cited by 196
Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin
Malito, E., Hulse, R. E., & Tang, W.-J. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8112-4 · Cited by 176

Flagged first, then by citations

Research works printed but not linked: 204

10.1371/journal.pone.0020818 · DOI
10.1016/j.jns.2010.09.030 · DOI
10.3233/JAD-2011-101716 · DOI
10.1007/BF02118312 · DOI
10.1016/S0304-3940(03)00030-2 · DOI · Paper page
10.1111/j.1471-4159.1982.tb07930.x · DOI
10.1096/fj.11-182154 · DOI
10.1186/1471-2164-12-160 · DOI
10.1016/j.gene.2011.06.017 · DOI
10.1016/j.brainres.2010.08.025 · DOI
10.1023/A:1022435111928 · DOI · Paper page
10.1111/j.1471-4159.1992.tb10950.x · DOI
10.1111/j.1527-3466.2005.tb00175.x · DOI
10.3233/JAD-2011-110746 · DOI
10.1038/embor.2008.222 · DOI
10.1074/jbc.M110.141390 · DOI
Blomqvist M. E., 2010, Evaluation of neprilysin sequence variation in relation to CSF β‐Amyloid levels and Alzheimer disease risk, Int. J. Mol. Epidemiol. Genet., 1, 47
10.1161/HYPERTENSIONAHA.107.098772 · DOI
10.3233/JAD-2010-1206 · DOI
10.1126/science.1058783 · DOI · Paper page
10.1093/jnen/61.10.849 · DOI
10.1128/MCB.24.10.4428-4437.2004 · DOI
10.1002/path.2885 · DOI
10.1016/j.bbr.2006.06.020 · DOI
Chen A. C., 2007, Response to: Pardossi‐Piquard et al.“Presenilin‐Dependent Transcriptional Control of the Aβ‐Degrading Enzyme Neprilysin by Intracellular Domains of βAPP and APLP.”, Neuron, 46, 541
10.1042/0264-6021:3510509 · DOI
10.1073/pnas.0509725103 · DOI
10.1016/j.jmb.2008.11.025 · DOI
10.1016/S0002-9440(10)63822-9 · DOI
10.1074/jbc.M109.026674 · DOI
10.1212/WNL.55.6.763 · DOI
10.1046/j.1471-4159.1996.66041641.x · DOI
10.1042/BST20051101 · DOI
10.1074/jbc.M007579200 · DOI
10.1074/jbc.C200642200 · DOI
10.1074/jbc.M111571200 · DOI
10.1091/mbc.E07-01-0035 · DOI
10.2353/ajpath.2008.070620 · DOI
10.1074/jbc.270.25.15262 · DOI
10.3233/JAD-2010-091633 · DOI
10.1111/j.1471-4159.2009.05894.x · DOI
10.1111/j.1471-4159.2011.07359.x · DOI
10.1016/S0306-4522(02)01002-3 · DOI
10.1074/jbc.M602532200 · DOI
10.1073/pnas.0230450100 · DOI
10.2174/156720511794604561 · DOI
Ferrington L., 2011, Angiotensin II‐inhibiting drugs have no effect on intraneuronal Aβ or oligomeric Aβ levels in a triple transgenic mouse model of Alzheimer’s disease, Am. J. Transl. Res., 3, 197
10.1042/bj2030519 · DOI
10.1042/0264-6021:3470419 · DOI
10.1016/j.bbabio.2009.12.016 · DOI
10.1242/jcs.048090 · DOI
10.1002/path.2594 · DOI
10.1002/jnr.21944 · DOI
10.1016/j.ajpath.2010.11.012 · DOI
10.1177/1533317507309803 · DOI
10.1093/oxfordjournals.jbchem.a003040 · DOI
10.1007/s12031-010-9460-8 · DOI
10.1007/s11064-006-9221-9 · DOI
10.1111/j.1471-4159.2009.06181.x · DOI · Paper page
10.1126/science.1566067 · DOI · Paper page
10.1007/s00401-011-0801-7 · DOI
10.1038/nature09325 · DOI
10.1038/sj.embor.7400704 · DOI
10.1016/j.neurobiolaging.2006.05.030 · DOI
10.1136/jnnp.2004.036574 · DOI
10.1074/jbc.M508460200 · DOI
10.1371/journal.pmed.0040262 · DOI
10.1016/j.nbd.2007.01.004 · DOI
10.1042/bj3270023 · DOI
10.1371/journal.pone.0021337 · DOI
Hong Y., 2011, The impact of amyloid precursor protein signalling and histone deacetylase inhibition on neprilysin expression in human prostate cells, Int. J. Cancer
10.1515/BC.2010.110 · DOI
10.1021/bi900037s · DOI
10.1016/0196-9781(95)00021-B · DOI
10.1016/S0304-3940(99)00827-7 · DOI
10.1074/jbc.M104068200 · DOI
10.1016/j.neuroscience.2008.05.006 · DOI
10.1074/jbc.M710509200 · DOI
10.1074/jbc.274.45.32469 · DOI
10.1074/jbc.M701590200 · DOI
10.1002/jnr.10390 · DOI
10.1073/pnas.0710823105 · DOI
10.1155/2009/384047 · DOI
10.1038/ng.2007.23 · DOI · Paper page
10.2174/156720509789207949 · DOI
10.1093/hmg/ddg094 · DOI
10.1007/s00439-004-1093-y · DOI
10.1042/bj1370477 · DOI
10.1159/000077132 · DOI
10.1210/en.2008-0524 · DOI
10.1038/npp.2009.197 · DOI · Paper page
10.1096/fj.09-148825 · DOI
10.4061/2011/857368 · DOI
Kiss A., 2006, Effect of Epilobium angustifolium L. extracts and polyphenols on cell proliferation and neutral endopeptidase activity in selected cell lines, Pharmazie, 61, 66
10.1523/JNEUROSCI.2985-10.2010 · DOI
Konietzko U., 2011, AICD Nuclear Signaling and its Possible Contribution to Alzheimer’s Disease, Curr. Alzheimer Res.
10.1016/j.neurobiolaging.2008.03.001 · DOI
10.1016/0014-5793(94)00387-4 · DOI · Paper page
10.1016/j.bbrc.2010.06.045 · DOI
10.1016/j.bbamcr.2011.09.014 · DOI
10.1093/embo-reports/kvd107 · DOI
10.1016/j.neulet.2007.06.037 · DOI
10.1074/jbc.R800022200 · DOI
10.1016/S0896-6273(03)00787-6 · DOI
10.1074/jbc.M305627200 · DOI
10.1042/BJ20041081 · DOI
10.1371/journal.pone.0010504 · DOI
10.1016/S0304-3940(02)00553-0 · DOI
10.1074/jbc.M109.050856 · DOI
10.1016/j.peptides.2007.09.015 · DOI
10.1038/mt.2009.115 · DOI
10.1016/j.mcn.2010.05.014 · DOI
10.1016/j.neurobiolaging.2009.06.003 · DOI
10.1016/S0022-510X(02)00398-2 · DOI
10.1016/j.neulet.2009.02.039 · DOI
10.1016/j.pneurobio.2011.06.006 · DOI
10.1523/JNEUROSCI.23-06-01992.2003 · DOI
10.1073/pnas.80.10.3111 · DOI
10.1523/JNEUROSCI.2984-08.2009 · DOI
10.1078/094471103322331449 · DOI
10.1038/ng.2007.29 · DOI
10.1111/j.1750-3639.2008.00132.x · DOI
10.1074/jbc.M202899200 · DOI
10.1016/j.bbrc.2005.05.020 · DOI
10.1016/j.neuron.2006.07.027 · DOI
10.1042/BJ20091941 · DOI
10.1074/jbc.M211242200 · DOI
10.1523/JNEUROSCI.20-05-02003.2000 · DOI
10.1196/annals.1332.002 · DOI
10.2174/156720508783954785 · DOI
10.1016/j.tips.2009.07.002 · DOI
10.1007/s12031-011-9644-x · DOI
10.1111/j.1471-4159.2011.07338.x · DOI
10.1074/jbc.M109.016683 · DOI
10.1371/journal.pone.0020864 · DOI
10.1111/j.1460-9568.2005.03912.x · DOI
10.1007/s11010-008-9747-z · DOI
10.1212/01.WNL.0000140705.23869.E9 · DOI
10.1096/fj.04-2637fje · DOI · Paper page
10.1124/mol.60.6.1332 · DOI
10.1006/bbrc.2000.2664 · DOI
10.2353/ajpath.2009.081054 · DOI
10.1111/j.1365-2990.2010.01084.x · DOI
10.1111/j.1471-4159.2011.07475.x · DOI · Paper page
10.1016/j.neuron.2005.04.008 · DOI
10.1016/j.biochi.2005.04.002 · DOI
10.1016/j.biocel.2008.12.015 · DOI
10.1016/j.neulet.2009.11.075 · DOI
10.1084/jem.20081588 · DOI
10.1074/jbc.273.49.32730 · DOI · Paper page
10.1074/jbc.M101703200 · DOI
10.1016/j.neurobiolaging.2008.05.033 · DOI
10.1523/JNEUROSCI.3467-10.2010 · DOI · Paper page
10.1006/bbrc.1994.2872 · DOI
10.1073/pnas.0701910104 · DOI
10.1038/288286a0 · DOI
10.1042/0264-6021:3630697 · DOI
10.1523/JNEUROSCI.4220-08.2009 · DOI
10.1016/j.neuroscience.2006.10.022 · DOI
10.1038/nm1206 · DOI
10.1159/000076351 · DOI
10.1124/mi.7.5.8 · DOI
10.1155/2008/578304 · DOI
10.1038/nm.1872 · DOI · Paper page
10.1042/bj3280871 · DOI
10.1016/0896-6273(91)90052-2 · DOI · Paper page
10.1111/j.1471-4159.2009.05950.x · DOI
10.1038/nature05143 · DOI
10.1016/j.bbrc.2004.08.231 · DOI
10.1074/jbc.M008511200 · DOI
10.1007/s10989-006-9034-3 · DOI
10.1016/j.neuroscience.2010.04.041 · DOI
10.1074/jbc.M308983200 · DOI
10.1371/journal.pone.0016575 · DOI
10.1016/j.ejphar.2008.03.058 · DOI
10.4088/JCP.09com05331 · DOI
10.1523/JNEUROSCI.20-11-03937.2000 · DOI
10.1515/bchm3.1995.376.4.225 · DOI
10.1096/fasebj.11.5.9141502 · DOI
10.1038/embor.2011.25 · DOI
10.1074/jbc.270.50.29794 · DOI
10.1046/j.1432-1327.1999.00602.x · DOI
10.1021/bi990610f · DOI
10.3233/JAD-2009-1002 · DOI
10.1016/j.neurobiolaging.2010.11.003 · DOI
Vaughan D. E., 2010, PAI‐1 antagonists: the promise and the peril, Trans. Am. Clin. Climatol. Assoc., 122, 312
10.1002/jcp.21743 · DOI
10.1016/j.neulet.2008.04.025 · DOI
10.1074/jbc.M407333200 · DOI
10.1016/j.yexcr.2008.05.003 · DOI
10.1016/j.yexcr.2006.10.028 · DOI
10.1111/j.1749-6632.2002.tb04812.x · DOI
10.1016/j.febslet.2008.05.046 · DOI
10.1074/jbc.M102790200 · DOI
10.1038/embor.2010.210 · DOI
10.1111/j.1471-4159.2006.04251.x · DOI
10.1186/1750-1326-4-33 · DOI
10.1523/JNEUROSCI.2085-06.2006 · DOI · Paper page
10.1016/j.brainresbull.2009.09.003 · DOI
10.1186/1750-1326-4-4 · DOI

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Self-citation

Authors: Nalivaeva, N. N., Beckett, C., Belyaev, N. D., & Turner, A. J.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2011-11-28
Volume: 120
Issue: s1
Pages: 167-185
ISSN: 0022-3042
1471-4159
DOI: 10.1111/j.1471-4159.2011.07510.x
Cited by: 169
References: 13
Language: en
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer’s disease?

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