The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology
Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer’s 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 conditio...
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/2075-1729/11/5/388 |
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| author | Mariona Jové Natàlia Mota-Martorell Pascual Torres Victoria Ayala Manuel Portero-Otin Isidro Ferrer Reinald Pamplona |
| author_facet | Mariona Jové Natàlia Mota-Martorell Pascual Torres Victoria Ayala Manuel Portero-Otin Isidro Ferrer Reinald Pamplona |
| author_sort | Mariona Jové |
| collection | DOAJ |
| description | Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer’s 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. |
| first_indexed | 2024-03-10T11:59:17Z |
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| id | doaj.art-c8b493336bdb43cbbdf3491ac111382b |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T11:59:17Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj.art-c8b493336bdb43cbbdf3491ac111382b2023-11-21T17:06:52ZengMDPI AGLife2075-17292021-04-0111538810.3390/life11050388The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease PathologyMariona Jové0Natàlia Mota-Martorell1Pascual Torres2Victoria Ayala3Manuel Portero-Otin4Isidro Ferrer5Reinald Pamplona6Department of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, SpainDepartment of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, SpainDepartment of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, SpainDepartment of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, SpainDepartment of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, SpainDepartment of Pathology and Experimental Therapeutics, University of Barcelona, Bellvitge University Hospital/Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, SpainDepartment of Experimental Medicine, Lleida Biomedical Research Institute (IRBLleida), Lleida University (UdL), 25198 Lleida, SpainCurrent shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer’s 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.https://www.mdpi.com/2075-1729/11/5/388agingATP synthaseenergy metabolismentorhinal cortexlipoxidation-derived damagemitochondrial dysfunction |
| spellingShingle | Mariona Jové Natàlia Mota-Martorell Pascual Torres Victoria Ayala Manuel Portero-Otin Isidro Ferrer Reinald Pamplona The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology Life aging ATP synthase energy metabolism entorhinal cortex lipoxidation-derived damage mitochondrial dysfunction |
| title | The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology |
| title_full | The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology |
| title_fullStr | The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology |
| title_full_unstemmed | The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology |
| title_short | The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology |
| title_sort | causal role of lipoxidative damage in mitochondrial bioenergetic dysfunction linked to alzheimer s disease pathology |
| topic | aging ATP synthase energy metabolism entorhinal cortex lipoxidation-derived damage mitochondrial dysfunction |
| url | https://www.mdpi.com/2075-1729/11/5/388 |
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