{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:52:23Z","timestamp":1790823143274,"version":"4.1.0"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:p>Mutations within the A\u03b2 (amyloid \u03b2) peptide, especially those clustered at residues 21\u201323, are linked to early-onset AD (Alzheimer's disease) and primarily associated with cerebral amyloid angiopathy. The Iowa variant, a substitution of an aspartic acid residue for asparagine at position 23 (D23N), associates with widespread vascular amyloid and abundant diffuse pre-amyloid lesions significantly exceeding the incidence of mature plaques. Brain Iowa deposits consist primarily of a mixture of mutated and non-mutated A\u03b2 species exhibiting partial aspartate isomerization at positions 1, 7 and 23. The present study analysed the contribution of the post-translational modification and the D23N mutation to the aggregation\/fibrillization and cell toxicity properties of A\u03b2 providing insight into the elicited cell death mechanisms. The induction of apoptosis by the different A\u03b2 species correlated with their oligomerization\/fibrillization propensity and \u03b2-sheet content. Although cell toxicity was primarily driven by the D23N mutation, all A\u03b2 isoforms tested were capable, albeit at different time frames, of eliciting comparable apoptotic pathways with mitochondrial engagement and cytochrome c release to the cytoplasm in both neuronal and microvascular endothelial cells. Methazolamide, a cytochrome c release inhibitor, exerted a protective effect in both cell types, suggesting that pharmacological targeting of mitochondria may constitute a viable therapeutic avenue.<\/jats:p>","DOI":"10.1042\/bj20130652","type":"journal-article","created":{"date-parts":[[2013,9,16]],"date-time":"2013-09-16T09:27:04Z","timestamp":1379323624000},"page":"347-360","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Differential contribution of isoaspartate post-translational modifications to the fibrillization and toxic properties of amyloid \u03b2 and the Asn23 Iowa mutation"],"prefix":"10.1042","volume":"456","author":[{"given":"Silvia","family":"Fossati","sequence":"first","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krysti","family":"Todd","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystal","family":"Sotolongo","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Ghiso","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, U.S.A."},{"name":"Department of Psychiatry, New York University School of Medicine, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agueda","family":"Rostagno","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2013,11,22]]},"reference":[{"key":"2021112215502661100_B1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00018-009-0182-4","article-title":"Cerebral amyloidosis: amyloid subunits, mutants and phenotypes","volume":"67","author":"Rostagno","year":"2010","journal-title":"Cell. 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