TDP-43 impairs glycolysis by sequestering hexokinase 1 in amyotrophic lateral sclerosis - PubMed
5 hours ago
- #TDP-43
- #ALS
- #glycolysis
- TDP-43 impairs glycolysis by sequestering hexokinase 1 (HK1) in ALS.
- Cytoplasmic TDP-43 accumulation reduces glycolytic capacity in neurons.
- HK1 protein levels, mitochondrial association, and activity decrease in ALS models despite unchanged transcript levels.
- TDP-43 binds to HK1, disassociating it from mitochondria and promoting its sequestration into insoluble aggregates.
- Compensation for HK1 loss reduces TDP-43 accumulation, improves motor performance, and prolongs survival in ALS models.
- Glycolytic restoration is highlighted as a potential therapeutic strategy in ALS.