Abstract
Oxidative stress has been consistently linked to ageing-related neurodegenerative diseases leading to the generation of lipid peroxides, carbonyl proteins and oxidative DNA damage in tissue samples from affected brains. Studies from mouse models that express disease-specific mutant proteins associated to the major neurodegenerative processes have underscored a critical role of mitochondria in the pathogenesis of these diseases. There is strong evidence that mitochondrial dysfunction is an early event in neurodegeneration. Mitochondria are the main cellular source of reactive oxygen species and key regulators of cell death. Moreover, mitochondria are highly dynamic organelles that divide, fuse and move along axons and dendrites to supply cellular energetic demands; therefore, impairment of any of these processes would directly impact on neuronal viability. Most of the disease-specific pathogenic mutant proteins have been shown to target mitochondria, promoting oxidative stress and the mitochondrial apoptotic pathway. In addition, disease-specific mutant proteins may also impair mitochondrial dynamics and recycling of damaged mitochondria via autophagy. Collectively, these data suggest that ROS-mediated defective mitochondria may accumulate during and contribute to disease progression. Strategies aimed to improve mitochondrial function or ROS scavenging may thus be of potential clinical relevance.
Keywords: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, oxidative stress, mitochondria, autophagy, mitochondrial dynamics
CNS & Neurological Disorders - Drug Targets
Title: Oxidative Stress and Altered Mitochondrial Function in Neurodegenerative Diseases: Lessons From Mouse Models
Volume: 9 Issue: 4
Author(s): J.C. Fernandez-Checa, A. Fernandez, A. Morales, M. Mari, C. Garcia-Ruiz and A. Colell
Affiliation:
Keywords: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, oxidative stress, mitochondria, autophagy, mitochondrial dynamics
Abstract: Oxidative stress has been consistently linked to ageing-related neurodegenerative diseases leading to the generation of lipid peroxides, carbonyl proteins and oxidative DNA damage in tissue samples from affected brains. Studies from mouse models that express disease-specific mutant proteins associated to the major neurodegenerative processes have underscored a critical role of mitochondria in the pathogenesis of these diseases. There is strong evidence that mitochondrial dysfunction is an early event in neurodegeneration. Mitochondria are the main cellular source of reactive oxygen species and key regulators of cell death. Moreover, mitochondria are highly dynamic organelles that divide, fuse and move along axons and dendrites to supply cellular energetic demands; therefore, impairment of any of these processes would directly impact on neuronal viability. Most of the disease-specific pathogenic mutant proteins have been shown to target mitochondria, promoting oxidative stress and the mitochondrial apoptotic pathway. In addition, disease-specific mutant proteins may also impair mitochondrial dynamics and recycling of damaged mitochondria via autophagy. Collectively, these data suggest that ROS-mediated defective mitochondria may accumulate during and contribute to disease progression. Strategies aimed to improve mitochondrial function or ROS scavenging may thus be of potential clinical relevance.
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Cite this article as:
Fernandez-Checa J.C., Fernandez A., Morales A., Mari M., Garcia-Ruiz C. and Colell A., Oxidative Stress and Altered Mitochondrial Function in Neurodegenerative Diseases: Lessons From Mouse Models, CNS & Neurological Disorders - Drug Targets 2010; 9 (4) . https://dx.doi.org/10.2174/187152710791556113
DOI https://dx.doi.org/10.2174/187152710791556113 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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