Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

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• 作者：Mohammed Akbar^a ; ¹ ; Musthafa Mohamed Essa^b ; ^c ; ¹ ; Ghazi Daradkeh^b ; ¹ ; Mohamed A. Abdelmegeed^a ; Youngshim Choi^a ; Lubna Mahmood^d ; Byoung-Joon Song^a ;
• 关键词：Aβ ; Amyloid-β ; α-Syn ; α-Synuclein ; AChEI ; Acetyl cholinesterase inhibitors ; AcLys ; Acetylated Lys ; AD ; Alzheimer׳s disease ; ALS ; Amyotrophic lateral sclerosis ; APOE ; APO-lipoprotein E ; APP ; Amyloid precursor protein ; BACE1 ; Beta-secretase ; CBP ; CREB-binding protein ; CMT ; Charcot&ndash ; Marie&ndash ; Tooth type 2A disease ; COX ; Cytochrome C oxidase ; Drp1 ; Dynamin-related protein-1 ; ER ; Endoplasmic reticulum ; FAD ; Familial Alzheimer׳s disease ; GAPDH ; Glyceraldehyde-3-phosphate dehydro
• 刊名：Brain Research
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：1637
• 期：Complete
• 页码：34-55
• 全文大小：925 K

文摘

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.