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Brain Res. 2016 Apr 15;1637:34-55. doi: 10.1016/j.brainres.2016.02.016. Epub 2016 Feb 13.

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress.

Author information

1
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.
2
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.
3
Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman.
4
Department of Nutritional Sciences, Qatar University, Qatar.

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.

KEYWORDS:

Antioxidants; Mitochondrial dysfunction; Neurodegenerative diseases; Neuronal cell death; Oxidative stress; Post-translational protein modifications; Translational research

PMID:
26883165
PMCID:
PMC4821765
DOI:
10.1016/j.brainres.2016.02.016
[Indexed for MEDLINE]
Free PMC Article

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