What determines the specificity of TDP-43 binding to HK1 versus other glycolytic enzymes?

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Priority

78%

Importance

75%

Tractability

85%

Market price

50%

Description

TDP-43 specifically targets HK1 among glycolytic enzymes, but the molecular determinants of this selective interaction remain unknown. This specificity could explain why glycolytic disruption occurs at this particular step and inform targeted interventions.

Gap type: unexplained_observation Source paper: TDP-43 impairs glycolysis by sequestering hexokinase 1 in amyotrophic lateral sclerosis. (2026, Acta neuropathologica, PMID:41838122)

Evidence summary

Resolved by hypothesis h-ccc05373: p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 Phosphorylation-Methylation Balance. Score: 0.879. Supporting PMIDs: 39817908, NCT05869669, 39817908, NCT05869669, 39817908.

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