The threat of instability: Neurodegeneration predicted by protein destabilization and aggregation propensity
2008

Protein Instability and Neurodegeneration in ALS

publication Evidence: moderate

Author Information

Author(s): Elizabeth M. Meiering

Primary Institution: University of Waterloo

Hypothesis

The study investigates the correlation between protein destabilization and patient survival in amyotrophic lateral sclerosis (ALS).

Conclusion

The study found a strong correlation between the aggregation propensity of mutant SOD1 proteins and decreased patient survival in ALS.

Supporting Evidence

  • Increased aggregation propensity of mutant SOD1 is significantly correlated with decreased patient survival.
  • Decreased stability of mutant SOD1 tends to be associated with decreased survival.
  • The correlation with survival accounts for 69% of the variability in ALS patient survival data.

Takeaway

This study shows that when certain proteins become unstable, it can lead to diseases like ALS, which makes patients not live as long.

Methodology

The study applied the Chiti-Dobson equation to calculate aggregation propensity for mutant SOD1 and correlated it with patient survival data.

Potential Biases

Variability in patient survival data may arise from age-dependent, environmental, and genetic factors.

Limitations

The analysis did not account for 100% of the SOD1 mutant patient data due to limitations in the amount and quality of available patient data.

Participant Demographics

The study analyzed data from ALS patients with various SOD1 mutations.

Statistical Information

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pbio.0060193

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication