Neurons accumulate DNA damage with age and in neurodegenerative diseases due to limited DNA repair capacity.
Neurons are post-mitotic and cannot use homologous recombination for DNA repair. They rely on base excision repair and NER.
- High transcriptional activity
- Age-related DNA damage accumulation
- Cognitive decline correlates
- Oxidative DNA damage
- Mitochondrial dysfunction
- 8-OHdG accumulation
- Early dysfunction in AD
- Transcription dysregulation
- Neuronal network deficits
- Oxidative lesions (8-OHdG)
- Single-strand breaks
- Double-strand breaks (aging)
- Telomere attrition
- Reduced BER capacity
- NER impairment with age
- Poly-ADP-ribose polymerase (PARP) overactivation
- Transcription dysfunction
- Genomic instability
- Cellular senescence
- PARP inhibitors
- BER enhancers
- NAD+ precursors
- Antioxidants
- Telomerase activation (controversial)
- Senolytics
- DNA damage in aging neurons (2022)
- DNA repair in neurodegeneration (2021)