{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:06:28Z","timestamp":1782914788265,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN-MIUR","award":["2017CY3J3W"],"award-info":[{"award-number":["2017CY3J3W"]}]},{"name":"PRIN-MIUR","award":["ARS01_01226"],"award-info":[{"award-number":["ARS01_01226"]}]},{"name":"Progetto PON-PerMedNet","award":["2017CY3J3W"],"award-info":[{"award-number":["2017CY3J3W"]}]},{"name":"Progetto PON-PerMedNet","award":["ARS01_01226"],"award-info":[{"award-number":["ARS01_01226"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The altered crosstalk between mitochondrial dysfunction, intracellular Ca2+ homeostasis, and oxidative stress has a central role in the dopaminergic neurodegeneration. In the present study, we investigated the hypothesis that pharmacological strategies able to improve mitochondrial functions might prevent neuronal dysfunction in in vitro models of Parkinson\u2019s disease. To this aim, the attention was focused on the amino acid ornithine due to its ability to cross the blood\u2013brain barrier, to selectively reach and penetrate the mitochondria through the ornithine transporter 1, and to control mitochondrial function. To pursue this issue, experiments were performed in human neuroblastoma cells SH-SY5Y treated with rotenone and 6-hydroxydopamine to investigate the pharmacological profile of the compound L-Ornithine-L-Aspartate (LOLA) as a new potential therapeutic strategy to prevent dopaminergic neurons\u2019 death. In these models, confocal microscopy experiments with fluorescent dyes measuring mitochondrial calcium content, mitochondrial membrane potential, and mitochondrial ROS production, demonstrated that LOLA improved mitochondrial functions. Moreover, by increasing NCXs expression and activity, LOLA also reduced cytosolic [Ca2+] thanks to its ability to modulate NO production. Collectively, these results indicate that LOLA, by interfering with those mitochondrial mechanisms related to ROS and RNS production, promotes mitochondrial functional recovery, thus confirming the tight relationship existing between cytosolic ionic homeostasis and cellular metabolism depending on the type of insult applied.<\/jats:p>","DOI":"10.3390\/cells11182909","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T22:12:43Z","timestamp":1663539163000},"page":"2909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["L-Ornithine L-Aspartate Restores Mitochondrial Function and Modulates Intracellular Calcium Homeostasis in Parkinson\u2019s Disease Models"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria Jos\u00e8","family":"Sisalli","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9650-7655","authenticated-orcid":false,"given":"Salvatore","family":"Della Notte","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-4098","authenticated-orcid":false,"given":"Agnese","family":"Secondo","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Ventra","sequence":"additional","affiliation":[{"name":"ESSETI Farmaceutici, 80046 San Giorgio a Cremano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Annunziato","sequence":"additional","affiliation":[{"name":"IRCCS Synlab SDN S.p.A, Via Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Scorziello","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nm.2165","article-title":"Missing pieces in the Parkinson\u2019s disease puzzle","volume":"16","author":"Obeso","year":"2010","journal-title":"Nat. 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