Review
Oxidative stress and mitochondrial dysfunction in Alzheimer's disease

https://doi.org/10.1016/j.bbadis.2013.10.015Get rights and content
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Highlights

  • Oxidative stress is an early and prominent feature of AD.

  • Structurally and functionally damaged mitochondria are characteristics of AD.

  • Mitochondrial fragmentation contributes to mitochondrial damage and dysfunction in AD.

  • A vicious downward spiral involving ROS and mitochondrial deficits is critical to AD pathogenesis.

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. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction and Neurodegenerative Diseases.

Abbreviations

(AD)
Alzheimer's disease
(Aβ)
amyloid-β
(APP)
amyloid-β protein precursor
(DS)
Down's syndrome
(DLP1)
dynamin-like protein 1 protein
(ER)
endoplasmic reticulum
(8-OHdG)
8-hydroxydeoxyguanosine
(8-OHG)
8-hydroxyguanosine
(MDA)
malondialdehyde
(MCI)
mild cognitive impairment
(mtDNA)
mitochondrial DNA
(Mfn1)
mitofusin 1
(Mfn2)
mitofusin 2
(NFTs)
neurofibrillary tangles
(OPA1)
optic atrophy protein 1
(ROS)
reactive oxygen species

Keywords

Alzheimer disease
Oxidative stress
Mitochondrial dysfunction
Mitochondrial fission
Mitochondrial fusion
DLP1

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This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction and Neurodegenerative Diseases.