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Review
. 2011 Nov;1812(11):1359-70.
doi: 10.1016/j.bbadis.2011.08.005. Epub 2011 Aug 18.

Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer's disease: implications for early intervention and therapeutics

Peizhong Mao  1 , P Hemachandra Reddy
Affiliations
Review

Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer's disease: implications for early intervention and therapeutics

Peizhong Mao et al. Biochim Biophys Acta. 2011 Nov.

Abstract

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease affecting thousands of people in the world and effective treatment is still not available. Over two decades of intense research using AD postmortem brains, transgenic mouse and cell models of amyloid precursor protein and tau revealed that amyloid beta (Aβ) and hyperphosphorylated tau are synergistically involved in triggering disease progression. Accumulating evidence also revealed that aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction initiate and contributes to the development and progression of the disease. The purpose of this article is to summarize the latest progress in aging and AD, with a special emphasis on the mitochondria, oxidative DNA damage including methods of its measurement. It also discusses the therapeutic approaches against oxidative DNA damage and treatment strategies in AD.

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Figures

Figure 1
Figure 1
Factors that are responsible for causing Alzheimer's disease (AD). Genetic mutations in amyloid precursor protein, presenilin 1 and presenilin 2 cause early-onset familial AD. Genetic variants in sortilin related receptor 1, clusterin, complement component receptor 1, CD2AP, CD33, EPHA1, &MS4A4/MS4A6E genes contribute to late-onset AD, in addition to ApoE 4/4 genotype. Aging, lifestyle activities and oxidative DNA damage are major contributing factors for the development of AD.
Figure 2
Figure 2
Protective therapeutic approaches that decrease oxidative DNA damage in aging and AD. 1. Mitochondria-targeted antioxidants, 2. Overexpression of mitochondria-localized sirtuins 3-5, 3. Mitochondria DNA repair enzymes, 4. Increased levels of insulin-like growth factor 1 and 5. Overexpression of nuclear transcription factors.
Figure 3
Figure 3
DNA repair mechanisms of mitochondrial and nuclear genomes.
See this image and copyright information in PMC

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