Study links mislocalized TDP-43 to impaired glycolysis in ALS models
Original source
TDP-43 impairs glycolysis by sequestering hexokinase 1 in amyotrophic lateral sclerosis. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human, Mouse
Related topics
A study found that cytoplasmic TDP-43 binds to hexokinase 1 (HK1), reducing its mitochondrial association and activity. This impaired glycolysis in patient-derived motor neurons, cellular models and mice, and was also observed in postmortem ALS spinal cord tissue. Restoring HK1 reduced disease-related changes and improved motor performance and survival in TDP-43-associated ALS mice.
Why this matters
The findings suggest that disrupted energy metabolism may contribute to motor neuron vulnerability in TDP-43-associated ALS. However, the work was conducted in cells, mice and postmortem tissue, so it does not currently change treatment for people with ALS. Restoring glycolysis would need to be tested for safety and benefit in human clinical studies.
Limitations and context
This is one primary research study. Its mechanistic and treatment findings are preclinical, based on cellular models and mice; the human material was postmortem spinal cord tissue. The study does not show that targeting HK1 benefits people with ALS, and the reported intervention has not been established as a human treatment.