NAD attenuates oxidative DNA damages induced by amyloid beta-peptide in primary rat cortical neurons

Abstract

One major pathological hallmark of Alzheimer's disease (AD) is accumulation of senile plaques in patients’ brains, mainly composed of amyloid beta-peptide (Aβ). Nicotinamide adenine dinucleotide (NAD) has emerged as a common mediator regulating energy metabolism, mitochondrial function, aging, and cell death, all of which are critically involved in neuronal demise observed in AD. In this work, we tested the hypothesis that NAD may attenuate Aβ-induced DNA damages, thereby conferring neuronal resistance to primary rat cortical cultures. We found that co-incubation of NAD dose-dependently attenuated neurotoxicity mediated by Aβ25–35 and Aβ1-42 in cultured rat cortical neurons, with the optimal protective dosage at 50 mM. NAD also abolished the formation of reactive oxygen species (ROS) induced by Aβ25-35. Furthermore, Aβs were capable of inducing oxidative DNA damages by increasing the extents of 8-hydroxy-2´-deoxyguanosine (8-OH-dG), numbers of apurinic/apyrimidinic (AP) sites, genomic DNA single-stranded breaks (SSBs), as well as DNA double-stranded breaks (DSBs)/fragmentation, which can all be attenuated upon co-incubation with NAD. Our results thus reveal a novel finding that NAD is protective against DNA damage induced by existing Aβ, leading ultimately to neuroprotection in primary cortical culture.

Keywords::

• 8-hydroxy-2´-deoxyguanosine
• Alzheimer's disease
• amyloid-beta
• DNA oxidation
• oxidative stress

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

The authors disclose no financial, consulting, and personal relationships with any other people or organizations that could influence this work. This study was supported by National Science Council in Taiwan (NSC 98-2314-B-010-020-MY3 and NSC 101-2314-B-010-042MY2 to Ding-I Yang), Ministry of Education in Taiwan-Aim for the Top University Plan (102AC-B5 to Ding-I Yang), Cheng Hsin General Hospital (102F218C12 to Ding-I Yang and Jiu-Haw Yin), Department of Health in Taipei City Government (10201-62-067 to Ding-I Yang and Chi-Shin Hwang), and Yen Tjing Ling Medical Foundation (CI-97-4 to Ding-I Yang).