Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Oxidative DNA damage contributes to mutagenesis, cancer, and neurological disorders.
• Base Excision Repair (BER) pathway repairs oxidative DNA damage.
• OGG1 initiates BER by excising 8-oxoguanine (8-oxoG), a major oxidative lesion.

Purpose of the Study:

• To review the development of OGG1 inhibitors and activators.
• To explore OGG1's fundamental roles beyond DNA repair.
• To discuss clinical applications and challenges in targeting OGG1.

Main Methods:

• Literature review of OGG1 inhibitors and activators.
• Analysis of OGG1's involvement in DNA repair, transcription, inflammation, and aging.
• Discussion of therapeutic strategies and challenges.

Main Results:

• OGG1 plays a crucial role in repairing oxidative DNA damage and modulating inflammation.
• Targeting OGG1 can enhance cancer therapy efficacy by sensitizing cells to treatments.
• OGG1 activators may mitigate oxidative stress in aging and neurological conditions.

Conclusions:

• Development of OGG1 modulators advances understanding of its functions.
• Targeting OGG1 presents therapeutic opportunities for cancer, inflammation, and neurological diseases.
• Addressing off-target effects is crucial for safe and effective OGG1-targeted therapies.