Chronic Oxidative Stress and Stress Granule Formation in UBQLN2 ALS Neurons: Insights into Neuronal Degeneration and Potential Therapeutic Targets
2024

Chronic Oxidative Stress and Stress Granule Formation in ALS Neurons

publication Evidence: moderate

Author Information

Author(s): Gu Ao, Zhang Yiti, He Jianfeng, Zhao Mingri, Ding Lingjie, Liu Wanxi, Xiao Jianing, Huang Jiali, Liu Mujun, Liu Xionghao, Zsindely Nora, Bodai Laszlo

Primary Institution: Central South University, Changsha, China

Hypothesis

Chronic oxidative stress contributes to neuronal degeneration in ALS through stress granule formation and abnormal protein aggregation.

Conclusion

The study found that oxidative stress exacerbates neuronal degeneration in ALS by promoting abnormal protein aggregation and stress granule formation.

Supporting Evidence

  • Oxidative stress was shown to increase stress granule formation in ALS neurons.
  • Chronic oxidative stress led to axonal swelling and neuronal death in the study's model.
  • Treatment with cycloheximide reduced stress granule formation and cell death under oxidative stress.
  • Bosutinib treatment improved cell viability in UBQLN2 mutant neurons.

Takeaway

This study shows that stress from aging and other factors can harm brain cells in ALS, and that certain treatments might help protect these cells.

Methodology

The study used induced motor neurons derived from UBQLN2 P497H iPSCs to investigate the effects of oxidative stress on neuronal degeneration.

Limitations

The study only tested a few drugs for rescuing neuronal pathology and did not conduct a high-throughput drug screen.

Digital Object Identifier (DOI)

10.3390/ijms252413448

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication