{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:06:35Z","timestamp":1788447995483,"version":"build-2803163510"},"reference-count":180,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T00:00:00Z","timestamp":1619308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/00757"],"award-info":[{"award-number":["PI14\/00757"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/00328"],"award-info":[{"award-number":["PI14\/00328"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/0155"],"award-info":[{"award-number":["PI20\/0155"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-099200-B-I00"],"award-info":[{"award-number":["RTI2018-099200-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002943","name":"Departament d'Innovaci\u00f3, Universitats i Empresa, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017SGR696"],"award-info":[{"award-number":["2017SGR696"]}],"id":[{"id":"10.13039\/501100002943","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer\u2019s disease (AD) pathology in the cerebrum. Compared with other cortical areas, the neurons from this brain region possess an inherent selective vulnerability derived from particular oxidative stress conditions that favor increased mitochondrial molecular damage with early bioenergetic involvement. This alteration of energy metabolism is the starting point for subsequent changes in a multitude of cell mechanisms, leading to neuronal dysfunction and, ultimately, cell death. These events are induced by changes that come with age, creating the substrate for the alteration of several neuronal pathways that will evolve toward neurodegeneration and, consequently, the development of AD pathology. In this context, the present review will focus on description of the biological mechanisms that confer vulnerability specifically to neurons of the entorhinal cortex, the changes induced by the aging process in this brain region, and the alterations at the mitochondrial level as the earliest mechanism for the development of AD pathology. Current findings allow us to propose the existence of an altered allostatic mechanism at the entorhinal cortex whose core is made up of mitochondrial oxidative stress, lipid metabolism, and energy production, and which, in a positive loop, evolves to neurodegeneration, laying the basis for the onset and progression of AD pathology.<\/jats:p>","DOI":"10.3390\/life11050388","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T22:31:39Z","timestamp":1619389899000},"page":"388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer\u2019s Disease Pathology"],"prefix":"10.3390","volume":"11","author":[{"given":"Mariona","family":"Jov\u00e9","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5937-7070","authenticated-orcid":false,"given":"Nat\u00e0lia","family":"Mota-Martorell","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7903-3478","authenticated-orcid":false,"given":"Pascual","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Ayala","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-0299","authenticated-orcid":false,"given":"Manuel","family":"Portero-Otin","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, Bellvitge University Hospital\/Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), ISCIII, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4337-6107","authenticated-orcid":false,"given":"Reinald","family":"Pamplona","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,25]]},"reference":[{"key":"ref_1","first-page":"483p","article-title":"World population ageing 1950\u20132050","volume":"XLIX","author":"Organisation","year":"2002","journal-title":"Popul. 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