Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1G93A) of ALS

Journal of Neuroinflammation, 2019 · DOI: https://doi.org/10.1186/s12974-019-1598-x · Published: September 23, 2019

Simple Explanation

This study investigates the potential of tempol, a cyclic nitroxide, as a therapeutic agent for amyotrophic lateral sclerosis (ALS). Tempol is known for its neuroprotective properties, and the study aimed to determine if it could improve lifespan and overall condition in mice with a genetic mutation associated with ALS. The research involved administering tempol to SOD1G93A transgenic mice, which are commonly used as a model for ALS. The treatment started at the asymptomatic phase and continued until the end stage of the disease. Researchers then evaluated neuronal survival, inflammation, and motor function. The results indicated that tempol treatment led to greater neuronal survival and reduced inflammation in the spinal cords of the treated mice. Additionally, the treated groups showed reduced expression of pro-inflammatory cytokines. These findings suggest that tempol has beneficial effects in delaying the onset of ALS by promoting neuronal survival and reducing glial cell reactivity.

Study Duration

7 weeks

Participants

SOD1G93A transgenic mice

Evidence Level

Level II: Animal Study

Key Findings

1
Tempol treatment promoted greater neuronal survival (23%) at the initial stage of symptoms compared to untreated animals, and this was maintained until the end stage.
2
The intense reactivity of astrocytes and microglia observed in untreated animals was reduced in the lumbar spinal cords of animals treated with tempol, indicating an immunomodulatory effect.
3
Tempol treatment resulted in reduced expression of pro-inflammatory cytokines (IL1β and TNFα) and a threefold decrease in the expression of TGFβ1 at the initial stage of symptoms compared with the control group.

Research Summary

This study investigated the therapeutic potential of tempol in SOD1G93A transgenic mice, a model for ALS. The results showed that tempol treatment enhanced neuronal survival and reduced glial cell reactivity during ALS progression. Tempol treatment was associated with reduced expression of pro-inflammatory cytokines and improved motor performance in the treated mice. This suggests that tempol has immunomodulatory and neuroprotective effects. The study concludes that tempol can be considered a promising drug for treating ALS due to its ability to improve immunomodulatory and anti-inflammatory effects, indicating therapeutic potential for this challenging neurodegenerative disease.

Practical Implications

Therapeutic Potential

Tempol shows promise as a potential therapeutic agent for ALS due to its neuroprotective and immunomodulatory effects.

Neuroinflammation Target

The study highlights the importance of targeting neuroinflammation in ALS treatment strategies and suggests tempol as a candidate for modulating glial cell reactivity.

Cytokine Modulation

Tempol's ability to downregulate pro-inflammatory cytokines indicates its potential in managing the inflammatory response associated with ALS.

Study Limitations

1
Tempol treatment did not show a statistically significant effect on the overall survival of ALS mice.
2
Conflicting results exist in the literature regarding the effects of tempol, potentially due to variations in protocol, strain, and gender.
3
Further studies are necessary to unveil the molecular basis of tempol and potential side effects of its chronic use.

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