A glycolytic shunt via the pentose phosphate pathway is a metabolic checkpoint for nervous system sensory homeostasis and axonal regeneration

Homeostasis and repair in the nervous system are thought to rely on distinct molecular programs. Here, we uncover an unexpected role for the pentose phosphate pathway (PPP) in peripheral sensory axons, where it supports both homeostatic mechanosensation and axonal regeneration after injury. We show that the PPP is enriched and active in sciatic nerve axoplasms, where it maintains redox balance via NADPH production, enabling physiological mechanical sensation. However, following sciatic nerve injury, the PPP is required for regeneration by fueling ribonucleotide synthesis through ribose-5-phosphate. In contrast, this pathway remains inactive after spinal cord injury (SCI), contributing to regenerative failure.…

• DM
  Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
• NI
  National Institute on Handicapped Research
• WF
  Wings for Life
• RT
  Rosetrees Trust
• MR
  Medical Research Council
• EA
  Engineering and Physical Sciences Research Council
• NI
  NIHR Imperial Biomedical Research Centre