| http://purl.uniprot.org/citations/36875692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36875692 | http://www.w3.org/2000/01/rdf-schema#comment | "IntroductionAlzheimer's disease (AD) is associated with amyloid β-protein 1-42 (Aβ42) accumulation in the brain. Aβ42 and Aβ40 are the major two species generated from amyloid precursor protein. We found that angiotensin-converting enzyme (ACE) converts neurotoxic Aβ42 to neuroprotective Aβ40 in an ACE domain- and glycosylation-dependent manner. Presenilin 1 (PS1) mutations account for most of cases of familial AD and lead to an increased Aβ42/40 ratio. However, the mechanism by which PSEN1 mutations induce a higher Aβ42/40 ratio is unclear.MethodsWe over expressed human ACE in mouse wild-type and PS1-deficient fibroblasts. The purified ACE protein was used to analysis the Aβ42-to-Aβ40- and angiotensin-converting activities. The distribution of ACE was determined by Immunofluorescence staining.ResultWe found that ACE purified from PS1-deficient fibroblasts exhibited altered glycosylation and significantly reduced Aβ42-to-Aβ40- and angiotensin-converting activities compared with ACE from wild-type fibroblasts. Overexpression of wild-type PS1 in PS1-deficient fibroblasts restored the Aβ42-to-Aβ40- and angiotensin-converting activities of ACE. Interestingly, PS1 mutants completely restored the angiotensin-converting activity in PS1-deficient fibroblasts, but some PS1 mutants did not restore the Aβ42-to-Aβ40-converting activity. We also found that the glycosylation of ACE in adult mouse brain differed from that of embryonic brain and that the Aβ42-to-Aβ40-converting activity in adult mouse brain was lower than that in embryonic brain.ConclusionPS1 deficiency altered ACE glycosylation and impaired its Aβ42-to-Aβ40- and angiotensin-converting activities. Our findings suggest that PS1 deficiency and PSEN1 mutations increase the Aβ42/40 ratio by reducing the Aβ42-to-Aβ40-converting activity of ACE."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.org/dc/terms/identifier | "doi:10.3389/fnagi.2023.1098034"xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Gao Y."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Islam S."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Nakamura T."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Tomita T."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Michikawa M."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/author | "Zou K."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/name | "Front Aging Neurosci"xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/pages | "1098034"xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/title | "Presenilin 1 deficiency impairs Abeta42-to-Abeta40- and angiotensin-converting activities of ACE."xsd:string |
| http://purl.uniprot.org/citations/36875692 | http://purl.uniprot.org/core/volume | "15"xsd:string |
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