title: Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress.
abstract: Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities.
authors.affiliation: Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akbar
authors.affiliation: Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Oman.
authors.forename: Musthafa Mohamed
authors.initials: MM
authors.lastname: Essa
authors.affiliation: Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Daradkeh
authors.affiliation: Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdelmegeed
authors.affiliation: Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Youngshim
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Nutritional Sciences, Qatar University, Qatar.
authors.forename: Lubna
authors.initials: L
authors.lastname: Mahmood
authors.affiliation: Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Byoung-Joon
authors.initials: BJ
authors.lastname: Song
mesh_terms: D000367:Age Factors; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D004272:DNA, Mitochondrial / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D018698:Glutamic Acid
keywords: Antioxidants; Mitochondrial dysfunction; Neurodegenerative diseases; Neuronal cell death; Oxidative stress; Post-translational protein modifications; Translational research