| Autor: |
Müller M; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Department of Medical Technology, Faculty of Medicine, Universidad de Chile, Santiago, Chile., Ahumada-Castro U; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Sanhueza M; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile., Gonzalez-Billault C; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile.; The Buck Institute for Research on Aging, Novato, CA, United States., Court FA; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; The Buck Institute for Research on Aging, Novato, CA, United States., Cárdenas C; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile.; Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.; Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States. |
| Abstrakt: |
Age is the main risk factor for the onset of neurodegenerative diseases. A decline of mitochondrial function has been observed in several age-dependent neurodegenerative diseases and may be a major contributing factor in their progression. Recent findings have shown that mitochondrial fitness is tightly regulated by Ca 2+ signals, which are altered long before the onset of measurable histopathology hallmarks or cognitive deficits in several neurodegenerative diseases including Alzheimer's disease (AD), the most frequent cause of dementia. The transfer of Ca 2+ from the endoplasmic reticulum (ER) to the mitochondria, facilitated by the presence of mitochondria-associated membranes (MAMs), is essential for several physiological mitochondrial functions such as respiration. Ca 2+ transfer to mitochondria must be finely regulated because excess Ca 2+ will disturb oxidative phosphorylation (OXPHOS), thereby increasing the generation of reactive oxygen species (ROS) that leads to cellular damage observed in both aging and neurodegenerative diseases. In addition, excess Ca 2+ and ROS trigger the opening of the mitochondrial transition pore mPTP, leading to loss of mitochondrial function and cell death. mPTP opening probably increases with age and its activity has been associated with several neurodegenerative diseases. As Ca 2+ seems to be the initiator of the mitochondrial failure that contributes to the synaptic deficit observed during aging and neurodegeneration, in this review, we aim to look at current evidence for mitochondrial dysfunction caused by Ca 2+ miscommunication in neuronal models of neurodegenerative disorders related to aging, with special emphasis on AD. |
