{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:19:45Z","timestamp":1768472385048,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"local institutional"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Presenilin 1 (PS1) is a transmembrane proteolytic subunit of \u03b3-secretase that cleaves amyloid precursor proteins. Mutations in PS1 (mPS1) are associated with early-onset familial Alzheimer\u2019s disease (AD). The link between mutated PS1, mitochondrial calcium regulation, and AD has been studied extensively in different test systems. Despite the wide-ranging role of mPS1 in AD, there is a paucity of information on the link between PS1 and neuronal cell death, a hallmark of AD. In the present study, we employed the selective mitochondrial uncoupler carbonyl cyanide chlorophenylhydrazone (CCCP) and compared the reactivity of mPS1-transfected cultured rat hippocampal neurons with PS1 and control neurons in a situation of impaired mitochondrial functions. CCCP causes a slow rise in cytosolic and mitochondrial calcium in all three groups of neurons, with the mPS1 neurons demonstrating a faster rise. Consequently, mPS1 neurons were depolarized by CCCP and measured with TMRM, a mitochondrial voltage indicator, more than the other two groups. Morphologically, CCCP produced more filopodia in mPS1 neurons than in the other two groups, which were similarly affected by the drug. Finally, mPS1 transfected neurons tended to die from prolonged exposure to CCCP sooner than the other groups, indicating an increase in vulnerability associated with a lower ability to regulate excess cytosolic calcium.<\/jats:p>","DOI":"10.3390\/ijms25010578","type":"journal-article","created":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T13:02:58Z","timestamp":1704114178000},"page":"578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6107-5052","authenticated-orcid":false,"given":"Liliia","family":"Kushnireva","sequence":"first","affiliation":[{"name":"Faculty of Biology, Perm State University, 614068 Perm, Russia"},{"name":"Department of Immunology and Regenerative Biology, The Weizmann Institute of Science, Rehovot 7610001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-0408","authenticated-orcid":false,"given":"Menahem","family":"Segal","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, The Weizmann Institute of Science, Rehovot 7610001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Korkotian","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, The Weizmann Institute of Science, Rehovot 7610001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15091","DOI":"10.1073\/pnas.1304171110","article-title":"Presenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons","volume":"110","author":"Wu","year":"2013","journal-title":"Proc. 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