{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:28:11Z","timestamp":1777598891700,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The AIF\/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase-independent mechanism. Inhibition of this complex in a model of glutamate-induced cell death in HT-22 neuronal cells by an AIF peptide (AIF(370-394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia-ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH-SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson\u2019s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370-394) confers resistance to STS-induced apoptosis in SH-SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF\/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF\/CypA complex is a promising target for developing novel therapeutic strategies against PD.<\/jats:p>","DOI":"10.3390\/ijms23010265","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T01:18:15Z","timestamp":1640654295000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Relevance of AIF\/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3622-1476","authenticated-orcid":false,"given":"Mariarosaria","family":"Conte","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Via L. De Crecchio 7, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, 80134 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Monti","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, 80134 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Via L. De Crecchio 7, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5374-3527","authenticated-orcid":false,"given":"Angela","family":"Nebbioso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Via L. De Crecchio 7, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-756X","authenticated-orcid":false,"given":"Menotti","family":"Ruvo","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, 80134 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7312-5387","authenticated-orcid":false,"given":"Lucia","family":"Altucci","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Via L. De Crecchio 7, 80138 Naples, Italy"},{"name":"Biogem, Institute of Molecular Biology and Genetics, Via Camporeale Area P.I.P., 83031 Ariano Irpino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nunzianna","family":"Doti","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, 80134 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y cell line in Parkinson\u2019s disease research: A systematic review","volume":"12","author":"Xicoy","year":"2017","journal-title":"Mol. 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