The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Angiotensin-converting Enzyme Degrades Alzheimer Amyloid β-Peptide (Aβ); Retards Aβ Aggregation, Deposition, Fibril Formation; and Inhibits Cytotoxicity
Open accessAbstract
We have demonstrated that the angiotensin-converting enzyme (ACE) genotype is associated with Alzheimer's disease (AD) in the Japanese population (). To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid beta-peptide (A beta) in vitro. Surprisingly, ACE was found to significantly inhibit A beta aggregation in a dose response manner. The inhibition of aggregation was specifically blocked by preincubation of ACE with an ACE inhibitor, lisinopril. ACE was confirmed to retard A beta fibril formation with electron microscopy. ACE inhibited A beta deposits on a synthaloid plate, which was used to monitor A beta deposition on autopsied brain tissue. ACE also significantly inhibited A beta cytotoxicity on PC12 h. The most striking fact was that ACE degraded A beta by cleaving A beta-(1-40) at the site Asp(7)-Ser(8). This was proven with reverse-phase HPLC, amino acid sequence analysis, and MALDI-TOF/MS. Compared with A beta-(1-40), aggregation and cytotoxic effects of the degradation products A beta-(1-7) and A beta-(8-40) peptides were reduced or virtually absent. These findings led to the hypothesis that ACE may affect susceptibility to AD by degrading A beta and preventing the accumulation of amyloid plaques in vivo.
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Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P., & Soubrier, F. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114844 · Cited by 3,767
Genetic associations with human longevity at the APOE and ACE loci
Schächter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., & Cohen, D. (1994) · Nature Genetics · doi:10.1038/ng0194-29 · Cited by 1,095
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
Cited by
Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.28 · Cited by 1,965
The Genetics of Alzheimer's Disease
Bertram, L., & Tanzi, R. E. (2012) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-385883-2.00008-4 · Cited by 760
Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747
The genetics of Alzheimer disease
Tanzi, R. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006296 · Cited by 727
Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease
Barage, S. H., & Sonawane, K. D. (2015) · Neuropeptides · doi:10.1016/j.npep.2015.06.008 · Cited by 579
Metadata
- Authors
- Hu, J., Igarashi, A., Kamata, M., & Nakagawa, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 276
- Issue
- 51
- Pages
- 47863-47868
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1569630040
- Cited by
- 360
- References
- 3
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Hu, J., Igarashi, A., Kamata, M., & Nakagawa, H. (2001). Angiotensin-converting Enzyme Degrades Alzheimer Amyloid β-Peptide (Aβ); Retards Aβ Aggregation, Deposition, Fibril Formation; and Inhibits Cytotoxicity. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m104068200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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