ALZHEIMERS RESEARCH PROJECT: Role of OGG1 in mitochondrial health

National Institute On Aging

Investigators

Abstract

DNA, the hereditary material, is constantly exposed to various endogenous and exogenous factors that can induce damage. Endogenous sources include metabolic byproducts and oxidative stress, while exogenous sources encompass environmental factors such as UV radiation and chemical agents. DNA damage can lead to mutations and genomic instability, posing a threat to cellular function and, in the long term, contributing to accelerated aging and neurodegeneration. 8-oxoguanine DNA glycosylase 1, OGG1, plays a crucial role in maintaining the integrity of DNA. OGG1 specifically targets and repairs a type of DNA damage known as 8-oxo guanine, and others, which arises from oxidative stress in both nuclear and mitochondrial DNA. As mitochondria are particularly susceptible to oxidative damage due to their involvement in energy production and exposure to reactive oxygen species, OGG1's helps in removing oxidative DNA damages and preserving the stability and functionality of mitochondrial DNA. By recognizing and excising damaged DNA bases, OGG1 contributes to the overall maintenance of mitochondrial genomic integrity, ensuring proper cellular function and health. Studies have suggested that OGG1 activity may decrease with age, and its impaired function could be linked to the accumulation of oxidative damage in DNA. This connection highlights the importance of OGG1 in maintaining genomic stability and preventing age-related cellular decline. Oxidative stress has been implicated in the pathogenesis of Alzheimer's, and OGG1's involvement in repairing DNA damage induced by oxidative stress suggests a potential link. This study seeks to explore the role OGG1 may have in Alzheimer's Disease progression.