{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:56:22Z","timestamp":1781326582612,"version":"3.54.1"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["Cacialli-RFO2024"],"award-info":[{"award-number":["Cacialli-RFO2024"]}]},{"DOI":"10.13039\/501100002426","name":"Telethon foundation","doi-asserted-by":"crossref","award":["Cacialli-GJC25P070"],"award-info":[{"award-number":["Cacialli-GJC25P070"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Familial Alzheimer\u2019s disease (FAD) is a rare form of Alzheimer\u2019s. FAD is mainly caused by one or multiple mutations in the genes encoding for amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), with the majority occurring in PSEN1. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for FAD. Recently, ZL006 (Med Chem Express cat. Number HY-100456) was shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke and could protect neurons against A\u03b21\u201342-induced neurotoxicity (in vitro study). With this in mind, we tested ZL006 at different doses (10 \u03bcM, 25 \u03bcM, 50 \u03bcM and 100 \u03bcM) in zebrafish embryo injected with ctrl-MO and psen1-MO, investigating the effects on pathological phenotype in vivo. We showed that ZL006 exposure suppresses inflammation, oxidative stress and accumulation of A\u03b21\u201342 in psen1-MO. In conclusion, our study showed that ZL006 was able to ameliorate the pathological phenotype of psen1-morphant zebrafish embryos, supporting its potential as a candidate for further investigations in the context of FAD treatment.<\/jats:p>","DOI":"10.3390\/ijms27114992","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZL006 Treatment Reduces Inflammation, Oxidative Stress, and Brain A\u03b21\u201342 Accumulation and Rescues the Loss of PSD95 Synaptic Marker in Familial Alzheimer\u2019s Disease-Associated psen1-Deficient Zebrafish Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Serena","family":"Ricci","sequence":"first","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences (BIGEA), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Benuzzi","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences (BIGEA), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5749-1898","authenticated-orcid":false,"given":"Martina","family":"Fazzina","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences (BIGEA), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-0793","authenticated-orcid":false,"given":"Pietro","family":"Cacialli","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences (BIGEA), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106961","DOI":"10.1016\/j.nbd.2025.106961","article-title":"Identification of presenilin mutations that have sufficient gamma-secretase proteolytic activity to mediate Notch signaling but disrupt organelle and neuronal health","volume":"212","author":"Ashkavand","year":"2025","journal-title":"Neurobiol. 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