{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:45:38Z","timestamp":1790811938488,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,18]],"date-time":"2022-12-18T00:00:00Z","timestamp":1671321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801073"],"award-info":[{"award-number":["81801073"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870844"],"award-info":[{"award-number":["81870844"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101394"],"award-info":[{"award-number":["82101394"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuritic plaques are one of the major pathological hallmarks of Alzheimer\u2019s disease. They are formed by the aggregation of extracellular amyloid-\u03b2 protein (A\u03b2), which is derived from the sequential cleavage of amyloid-\u03b2 precursor protein (APP) by \u03b2- and \u03b3-secretase. BACE1 is the main \u03b2-secretase in the pathogenic process of Alzheimer\u2019s disease, which is believed to be a rate-limiting step of A\u03b2 production. Presenilin 1 (PS1) is the active center of the \u03b3-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene (PSEN1) are the most common cause of early onset familial Alzheimer\u2019s disease (FAD). The PSEN1 mutations can alter the activity of \u03b3-secretase on the cleavage of APP. Previous studies have shown that PSEN1 mutations increase the expression and activity of BACE1 and that BACE1 expression and activity are elevated in the brains of PSEN1 mutant knock-in mice, compared with wild-type mice, as well as in the cerebral cortex of FAD patients carrying PSEN1 mutations, compared with sporadic AD patients and controls. Here, we used a Psen1 knockout cell line and a PS1 inhibitor to show that PS1 affects the expression of BACE1 in vitro. Furthermore, we used sucrose gradient fractionation combined with western blotting to analyze the distribution of BACE1, combined with a time-lapse technique to show that PS1 upregulates the distribution and trafficking of BACE1 in the endoplasmic reticulum, Golgi, and endosomes. More importantly, we found that the PSEN1 mutant S170F increases the distribution of BACE1 in the endoplasmic reticulum and changes the ratio of mature BACE1 in the trans-Golgi network. The effect of PSEN1 mutations on BACE1 may contribute to determining the phenotype of early onset FAD.<\/jats:p>","DOI":"10.3390\/ijms232416151","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:25:46Z","timestamp":1671427546000},"page":"16151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["PS1 Affects the Pathology of Alzheimer\u2019s Disease by Regulating BACE1 Distribution in the ER and BACE1 Maturation in the Golgi Apparatus"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-6064","authenticated-orcid":false,"given":"Nuomin","family":"Li","sequence":"first","affiliation":[{"name":"School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China"},{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjie","family":"Qiu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-450X","authenticated-orcid":false,"given":"Hong","family":"Qing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/alzrt211","article-title":"The role of APP and BACE1 trafficking in APP processing and amyloid-\u03b2 generation","volume":"5","author":"Zhang","year":"2013","journal-title":"Alzheimer\u2019s Res. 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