{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T04:17:11Z","timestamp":1748405831500,"version":"3.41.0"},"reference-count":22,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"The Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","award":["118S688"],"award-info":[{"award-number":["118S688"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Projects Coordination Unit at Hacettepe University","award":["19683"],"award-info":[{"award-number":["19683"]}]},{"name":"Scientific Projects Coordination Unit at Hacettepe University","award":["19929"],"award-info":[{"award-number":["19929"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Aggregations of unfolded or misfolded proteins, both inside and outside cells, are implicated in numerous diseases, collectively known as amyloidosis. Particularly, autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare disease caused by mutations in the AVP-NPII gene, leading to the inability to secrete arginine vasopressin. These misfolded proteins accumulate within the endoplasmic reticulum (ER), causing cellular dysfunction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study aimed to investigate the formation of amyloid-like aggregates within the cell resulting from misfolded mutant precursor proteins, which induce disulfide-linked oligomers due to the G45C, 207_209delGGC, G88V, C98X, C104F, E108D-1, E108D-2 and R122H mutations identified by our group in the AVP-NPII gene of ADNDI patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Deglycosylation studies were performed to analyze the glycosylation patterns of mutant protein precursors. The involvement of these precursors in the ER-related degradation pathway was studied by conducting protease inhibition experiments. Disulfide-linked oligomer analysis determined the oligomerization status of the mutant precursors. Immunofluorescence and electron microscopy studies provided evidence of aggregate structures in the ER lumen. In vitro studies involved bacterial expression and fibril formation in Escherichia coli (E. coli).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our findings demonstrated that the N-glycan structure of mutant precursors remains intact within the ER. Protease inhibition experiments indicated the involvement of these precursors in the ER-related degradation pathway. Disulfide-linked oligomer analysis revealed homo-oligomer structures in mutations. Immunofluorescence and electron microscopy studies confirmed the presence of aggregate structures in the ER lumen. In vitro studies showed that mutant precursors could form fibril structures in E. coli.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study may support the idea that ADNDI belongs to the group of neurodegenerative diseases due to the formation of fibrillar amyloid aggregates in the cell.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae749","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T08:02:04Z","timestamp":1729843324000},"page":"1577-1586","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Fibrillar Aggregates Formed by Pathogenic Pre-pro-vasopressin Mutants that Cause ADNDI"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-0954","authenticated-orcid":false,"given":"Refika Dilara","family":"Vaizoglu","sequence":"first","affiliation":[{"name":"Department of Biology, Universities District, Hacettepe University, Faculty of Science, Molecular Biology Section , Beytepe Campus, Cankaya\/Ankara 06800 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-1147","authenticated-orcid":false,"given":"Beril","family":"Erdem","sequence":"additional","affiliation":[{"name":"Department of Biology, Universities District, Hacettepe University, Faculty of Science, Molecular Biology Section , Beytepe Campus, Cankaya\/Ankara 06800 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-0783","authenticated-orcid":false,"given":"Mehmet","family":"Gul","sequence":"additional","affiliation":[{"name":"Inonu University, Faculty of Medicine, Basic Medical Sciences, Histology and Embryology Section , Malatya 44280 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1842-9203","authenticated-orcid":false,"given":"Ceren","family":"Acar","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Inonu University, Faculty of Arts and Science , Malatya 44280 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3284-5185","authenticated-orcid":false,"given":"Huseyin Ozgur","family":"Ozdemirel","sequence":"additional","affiliation":[{"name":"Department of Biology, Universities District, Hacettepe University, Faculty of Science, Molecular Biology Section , Beytepe Campus, Cankaya\/Ankara 06800 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-827X","authenticated-orcid":false,"given":"Emel","family":"Saglar Ozer","sequence":"additional","affiliation":[{"name":"Department of Biology, Universities District, Hacettepe University, Faculty of Science, Molecular Biology Section , Beytepe Campus, Cankaya\/Ankara 06800 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4606-2963","authenticated-orcid":false,"given":"Hatice","family":"Mergen","sequence":"additional","affiliation":[{"name":"Department of Biology, Universities District, Hacettepe University, Faculty of Science, Molecular Biology Section , Beytepe Campus, Cankaya\/Ankara 06800 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"2025052712592834700_dgae749-B1","first-page":"299","article-title":"Hereditary neurohypophyseal diabetes insipidus","volume":"111","author":"Rutishauser","year":"2019","journal-title":"Exp Suppl"},{"issue":"1","key":"2025052712592834700_dgae749-B2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41572-019-0103-2","article-title":"Diabetes insipidus","volume":"5","author":"Christ-Crain","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2025052712592834700_dgae749-B3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/bs.vh.2019.08.014","article-title":"Amyloid-like aggregation of provasopressin","volume":"113","author":"Spiess","year":"2020","journal-title":"Vitam Horm"},{"author":"P.D.Stenson HGMD\u00ae Copyright \u00a9 Cardiff University 2023","key":"2025052712592834700_dgae749-B4"},{"issue":"8","key":"2025052712592834700_dgae749-B5","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1172\/JCI119357","article-title":"Molecular basis of autosomal dominant neurohypophyseal diabetes insipidus. 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