Dna Damage Response And Repair In Neurodegeneration is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The DNA damage response (DDR) is a critical cellular mechanism that maintains genomic integrity. Accumulating evidence links impaired DNA repair to aging and neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (FTD), and Huntington's disease (HD)[1]. [2]
Neurons are particularly vulnerable to DNA damage due to: [3]
--- [4]
--- [5]
Primary pathway for oxidative damage [6]
In neurodegeneration: [7]
Bulky lesions, UV damage
In neurodegeneration:
Replication errors, small loops
In neurodegeneration:
In neurodegeneration:
| Protein | Function | Disease Association |
|---|---|---|
| ATM | DSB sensing, cell cycle arrest | Ataxia-telangiectasia, PD risk |
| ATR | Replication stress response | ALS, HD |
| PARP1 | SSB repair, DNA damage signaling | PD, AD |
| OGG1 | BER glycosylase for 8-oxoG | PD, aging |
| TDP-43 | RNA/DNA binding, DNA repair | ALS, FTD |
| FUS | RNA processing, DNA repair | ALS, FTD |
| C9orf72 | DNA damage response | ALS/FTD |
The study of Dna Damage Response And Repair In Neurodegeneration has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Recent publications advancing our understanding of this mechanism:
Roles of NAD(+) in Health and Aging. (2024) — Cold Spring Harb Perspect Med PMID:37848251
The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases. (2024) — Neurobiol Dis PMID:39490400
DNA repair deficiencies and neurodegeneration. (2024) — DNA Repair (Amst) PMID:38640601
Poly ADP-ribose signaling is dysregulated in Huntington disease. (2024) — Proc Natl Acad Sci U S A PMID:39331414
Crosstalk between the DNA damage response and cellular senescence drives aging and age-related diseases. (2024) — Semin Immunopathol PMID:39095660
🔴 Low Confidence
| Dimension | Score |
|---|---|
| Supporting Studies | 7 references |
| Replication | 33% |
| Effect Sizes | 25% |
| Contradicting Evidence | 0% |
| Mechanistic Completeness | 50% |
Overall Confidence: 32%
[1] Madabhushi R, Pan L, Tsai LH. DNA damage and its links to neurodegeneration. Neuron. 2014. ↩︎
[2] Fukushima T, et al. Association between OGG1 Ser326Cys polymorphism and Parkinson's disease. Arch Neurol. 2008. ↩︎ ↩︎
[3] Strosznajder JB, et al. Poly(ADP-ribose) polymerase-1 in DNA damage response and neurodegeneration. J Neurochem. 2012. ↩︎ ↩︎
[4] Katyal S, et al. DNA damage signaling in neurons. Nat Rev Neurosci. 2014. ↩︎
[5] Guo Z, et al. DNA repair in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2018. ↩︎
[6] Huber A, et al. TDP-43 and DNA damage in ALS. Brain. 2020. ↩︎
[7] Couve A, et al. DNA repair in Huntington's disease. J Huntingtons Dis. 2021. ↩︎