Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis
Abstract
1. Introduction
2. Pathogenesis Due to Toxic RNA Foci
3. Pathogenesis Due to Toxic DPRs
3.1. Translational Inhibition and Nucleic Acid Repair
3.2. Induction of Oxidative Stress
3.3. Inhibition of Ubiquitin-Proteasome and Autophagy
3.4. Induction of Inflammation
3.5. Impairment of Nucleocytoplasmic Transport (NCT)
3.6. The Dysfunction of Synapses
4. Pathogenesis Due to the Loss of C9ORF7 Function
4.1. Impairment of Autophagy
4.2. Dysfunction of NCT
4.3. ER Stress
4.4. Inflammation
5. Targeting C9orf722 HRE for Potential Therapeutic Strategies
5.1. Targeting RNA Repeats and DRPs
5.1.1. ASOs
5.1.2. Gene Editing (CRISPR/Cas9)
5.1.3. Small Molecules
5.2. Targeting Oxidative Stress
5.3. Autophagic Modulators
5.4. Targeting Neuromuscular Junction (NMJ)
5.5. Targeting NCT
5.6. Targeting Inflammation
6. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Chong, Z.Z.; Souayah, N. Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci. 2025, 26, 4276. https://doi.org/10.3390/ijms26094276
Chong ZZ, Souayah N. Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis. International Journal of Molecular Sciences. 2025; 26(9):4276. https://doi.org/10.3390/ijms26094276
Chicago/Turabian StyleChong, Zhao Zhong, and Nizar Souayah. 2025. "Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis" International Journal of Molecular Sciences 26, no. 9: 4276. https://doi.org/10.3390/ijms26094276
APA StyleChong, Z. Z., & Souayah, N. (2025). Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis. International Journal of Molecular Sciences, 26(9), 4276. https://doi.org/10.3390/ijms26094276