{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:49:58Z","timestamp":1791298198749,"version":"4.1.0"},"reference-count":199,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T00:00:00Z","timestamp":1722729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Scientifica di Ateneo"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca2+ ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca2+ are compromised, leading to Ca2+-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss. Recent research efforts directed toward understanding the pathology of PD have yielded significant insights, particularly highlighting the close relationship between Ca2+ dysregulation, neuroinflammation, and neurodegeneration. However, the precise mechanisms driving the selective loss of dopaminergic neurons in PD remain elusive. The disruption of Ca2+ homeostasis is a key factor, engaging various neurodegenerative and neuroinflammatory pathways and affecting intracellular organelles that store Ca2+. Specifically, impaired functioning of mitochondria, lysosomes, and the endoplasmic reticulum (ER) in Ca2+ metabolism is believed to contribute to the disease\u2019s pathophysiology. The Na+-Ca2+ exchanger (NCX) is considered an important key regulator of Ca2+ homeostasis in various cell types, including neurons, astrocytes, and microglia. Alterations in NCX activity are associated with neurodegenerative processes in different models of PD. In this review, we will explore the role of Ca2+ dysregulation and neuroinflammation as primary drivers of PD-related neurodegeneration, with an emphasis on the pivotal role of NCX in the pathology of PD. Consequently, NCXs and their interplay with intracellular organelles may emerge as potentially pivotal players in the mechanisms underlying PD neurodegeneration, providing a promising avenue for therapeutic intervention aimed at halting neurodegeneration.<\/jats:p>","DOI":"10.3390\/cells13151301","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T07:37:30Z","timestamp":1722843450000},"page":"1301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Calcium Deregulation in Neurodegeneration and Neuroinflammation in Parkinson\u2019s Disease: Role of Calcium-Storing Organelles and Sodium\u2013Calcium Exchanger"],"prefix":"10.3390","volume":"13","author":[{"given":"Guendalina","family":"Bastioli","sequence":"first","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7608-5589","authenticated-orcid":false,"given":"Silvia","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-5217","authenticated-orcid":false,"given":"Laura","family":"Graciotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Carone","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"},{"name":"Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8092 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Sprega","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0633-2117","authenticated-orcid":false,"given":"Omayema","family":"Taoussi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-2023","authenticated-orcid":false,"given":"Alessandra","family":"Preziuso","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasqualina","family":"Castaldo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, School of Medicine, University \u201cPolitecnica Delle Marche\u201d, Via Tronto 10\/A, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guzman-Martinez, L., Maccioni, R.B., Andrade, V., Navarrete, L.P., Pastor, M.G., and Ramos-Escobar, N. 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