DNA Damage and Impairment of DNA Repair in Alzheimer's Disease

Abstract

Deoxyribonucleic acid (DNA) damage has been implicated in ageing and neurodegenerative disorders including Alzheimer's disease (AD) for a few decades. Although it is an established finding, yet there are limited studies on DNA damage. In both nucleus and mitochondria, DNA damage is primarily free radical mediated. It has been proven that mitochondrial DNA is more vulnerable to damage compared to the nuclear DNA. A few studies summarized in this review throw light on the mechanisms of free radical mediated DNA damage and impairment of DNA repair mechanisms in AD. There is a growing need to initiate studies on DNA damage and repair and unravel the molecular underpinnings entailed in the etiopathogenesis of the disease. The outcome of such studies substantiates the corner stone streamlined to employ therapeutic strategies.

Tau Mediated Neurodegeneration: An Insight into Alzheimer’s Disease Pathology

“…Extracellular deposition of beta amyloid, intracellular NFT formation and oxidative stress induced by impaired metabolic pathways and metals are the hallmarks of AD [1][2][3][4][5]. Wealth of studies showed more than 4 decades ago that microtubule-based axonal transport and synaptic function might be impaired in AD [6][7][8][9].…”

Involvement of Histone PTMs in DNA Repair Processes in Relation to Age-Associated Neurodegenerative Disease

“…The transition from G0 to G1 was required for NHEJ repair in neurons (Tomashevski et al, 2010). In the brains of AD patients, the cell cycle of neurons could progress as far as the G2 phase, which was also required for repairing DNA lesions (Obulesu & Rao, 2010). Dynamic change of histone PTMs during cell cycle has been analyzed in HeLa cells (Bonenfant et al, 2007).…”

Mitochondrial DNA Repair

“…Increasing evidence also suggests that mitochondrial DNA damage accumulates with age. However conflicting reports argue whether aging is due to the accumulation of mitochondrial DNA damage or perhaps modifications in mitochondrial DNA repair mechanisms may cause accumulation of DNA damage associated with aging (Boesch et al, 2011;Gruber et al, 2008;Obulesu and Rao, 2010).…”