PIK3CA Gain-Of-Function Mutation In Schwann Cells Leads To Severe Neuropathy And Aerobic Glycolysis Through A Non-Cell Autonomous Effect

This study examines the impact of PIK3CA gain-of-function mutations in Schwann cells, leading to severe neuropathy and increased aerobic glycolysis through non-cell autonomous effects. Using a mouse model, researchers observed significant nerve enlargement, reduced myelinated fiber density, and abnormal myelination, with symptoms such as tremors and difficulty walking. The mutation activates the AKT/mTOR pathway, causing hypertrophy and increased skin thickness. Despite being restricted to Schwann cells, the mutation affects surrounding tissues, as seen in human biopsies. Early treatment with alpelisib, a PIK3CA inhibitor, improves outcomes, highlighting the importance of timely intervention and providing insights into potential therapeutic strategies.