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Review
. 2014 Aug;1842(8):1240-7.
doi: 10.1016/j.bbadis.2013.10.015. Epub 2013 Nov 1.

Oxidative stress and mitochondrial dysfunction in Alzheimer's disease

Xinglong Wang  1 , Wenzhang Wang  2 , Li Li  2 , George Perry  3 , Hyoung-gon Lee  2 , Xiongwei Zhu  4
Affiliations
Review

Oxidative stress and mitochondrial dysfunction in Alzheimer's disease

Xinglong Wang et al. Biochim Biophys Acta. 2014 Aug.

Abstract

Alzheimer's disease (AD) exhibits extensive oxidative stress throughout the body, being detected peripherally as well as associated with the vulnerable regions of the brain affected in disease. Abundant evidence not only demonstrates the full spectrum of oxidative damage to neuronal macromolecules, but also reveals the occurrence of oxidative events early in the course of the disease and prior to the formation of the pathology, which support an important role of oxidative stress in AD. As a disease of abnormal aging, AD demonstrates oxidative damage at levels that significantly surpass that of elderly controls, which suggests the involvement of additional factor(s). Structurally and functionally damaged mitochondria, which are more proficient at producing reactive oxygen species but less so in ATP, are also an early and prominent feature of the disease. Since mitochondria are also vulnerable to oxidative stress, it is likely that a vicious downward spiral involving the interactions between mitochondrial dysfunction and oxidative stress contributes to the initiation and/or amplification of reactive oxygen species that is critical to the pathogenesis of AD.

Keywords: Alzheimer disease; DLP1; Mitochondrial dysfunction; Mitochondrial fission; Mitochondrial fusion; Oxidative stress.

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Figures

Figure 1
Figure 1
Mitochondrial dysfunction is likely involved in the initiation and/or amplification of oxidative stress during the onset and progression of Alzheimer disease. Oxidative stress can negatively impact mitochondrial integrity and function. Defects in mitochondrial dynamics, either due to the response to genetic deficits or metabolic or environmental alterations, will make mitochondria less versatile in responding to the changing needs of neurons which will exacerbate mitochondrial dysfunction in chronic condition. The resultant mitochondrial dysfunction and ensuing greater oxidative stress and their interactions have the potential to form a vicious downward spiral that becomes a ubiquitous causative feature of cell malfunction, insufficient compensation and degeneration in AD.
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