{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T18:34:13Z","timestamp":1769279653153,"version":"3.49.0"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In Alzheimer\u2019s disease (AD), the molecular mechanisms involved in the neurodegeneration are still incompletely defined, though this aspect is crucial for a better understanding of the malady and for devising effective therapies. Mitochondrial dysfunctions and altered Ca2+ signaling have long been implicated in AD, though it is debated whether these events occur early in the course of the pathology, or whether they develop at late stages of the disease and represent consequences of different alterations. Mitochondria are central to many aspects of cellular metabolism providing energy, lipids, reactive oxygen species, signaling molecules for cellular quality control, and actively shaping intracellular Ca2+ signaling, modulating the intensity and duration of the signal itself. Abnormalities in the ability of mitochondria to take up and subsequently release Ca2+ could lead to changes in the metabolism of the organelle, and of the cell as a whole, that eventually result in cell death. We sought to investigate the role of mitochondria and Ca2+ signaling in a model of Familial Alzheimer\u2019s disease and found early alterations in mitochondria physiology under stressful condition, namely, reduced maximal respiration, decreased ability to sustain membrane potential, and a slower return to basal matrix Ca2+ levels after a mild excitotoxic stimulus. Treatment with an inhibitor of the permeability transition pore attenuated some of these mitochondrial disfunctions and may represent a promising tool to ameliorate mitochondria and cellular functioning in AD and prevent or slow down cell loss in the disease.<\/jats:p>","DOI":"10.3390\/cells10082046","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T08:57:14Z","timestamp":1628585834000},"page":"2046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Mild Excitotoxic Stimulus on Mitochondria Ca2+ Handling in Hippocampal Cultures of a Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Giulia","family":"Rigotto","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-8155","authenticated-orcid":false,"given":"Lorena","family":"Zentilin","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tullio","family":"Pozzan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"},{"name":"Neuroscience Institute, National Research Council (CNR), 35131 Padua, Italy"},{"name":"Venetian Institute of Molecular Medicine (VIMM), 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-7213","authenticated-orcid":false,"given":"Emy","family":"Basso","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"},{"name":"Neuroscience Institute, National Research Council (CNR), 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jalz.2019.04.001","article-title":"Duration of preclinical, prodromal, and dementia stages of Alzheimer\u2019s disease in relation to age, sex, and APOE genotype","volume":"15","author":"Vermunt","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. 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