{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:38:01Z","timestamp":1790411881485,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,8,7]],"date-time":"2012-08-07T00:00:00Z","timestamp":1344297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Mutations in amyloid precursor protein (APP), and presenilin\u20101 and presenilin\u20102 (PS1 and PS2) have causally been implicated in Familial Alzheimer\u2019s Disease (FAD), but the mechanistic link between the mutations and the early onset of neurodegeneration is still debated. Although no consensus has yet been reached, most data suggest that both FAD\u2010linked PS mutants and endogenous PSs are involved in cellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis. We here investigated subcellular Ca\n                    <jats:sup>2+\u2003<\/jats:sup>\n                    handling in primary neuronal cultures and acute brain slices from wild type and transgenic mice carrying the FAD\u2010linked PS2\u2010N141I mutation, either alone or in the presence of the APP Swedish mutation. Compared with wild type, both types of transgenic neurons show a similar reduction in endoplasmic reticulum (ER) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    content and decreased response to metabotropic agonists, albeit increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release induced by caffeine. In both transgenic neurons, we also observed a higher ER\u2013mitochondria juxtaposition that favors increased mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake upon ER Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. A model is described that integrates into a unifying hypothesis the contradictory effects on Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis of different PS mutations and points to the relevance of these findings in neurodegeneration and aging.\n                  <\/jats:p>","DOI":"10.1111\/j.1474-9726.2012.00858.x","type":"journal-article","created":{"date-parts":[[2012,7,17]],"date-time":"2012-07-17T06:13:52Z","timestamp":1342505632000},"page":"885-893","source":"Crossref","is-referenced-by-count":89,"title":["Ca\n                    <sup>2+<\/sup>\n                    dysregulation in neurons from transgenic mice expressing mutant presenilin 2"],"prefix":"10.1111","volume":"11","author":[{"given":"Maulilio J.","family":"Kipanyula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Contreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Zampese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Lazzari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea K. 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