Pharmacology network-based drug repurposing for CMT1A disease. For detailed explanations and abbreviations, see Additional file 1. (A) Three principal pathways regulating expression of PMP22 gene through extracellular GPCR signalling in Schwann cells. The functional interaction between cAMP pathway, neurosteroid-mediated signalling and PI3K-AKT/ERK kinase cascades, activated by receptor tyrosine kinases, control the expression of PMP22 gene in Schwann cells. Individual drugs are shown in green. Blue shading: cAMP pathway; green shading: neurosteroid-mediated signalling; yellow shading: RTK/PI3K-AKT/ERK kinase cascades. (B) Cytoprotective and neuromodulator actions of PXT3003 drug combination in peripheral neurons. Dysfunction of CMT1A Schwann cells could affect membrane excitability of neuronal cells, leading to abnormal processing of neuronal information, cytotoxicity and axonal loss. GPCRs, modulated by PXT3003 drugs, are well-known regulators of neuronal excitability and pain sensation, are able to activate cytoprotective signalling pathways in different experimental settings, and could preserve functional integrity of peripheral neurons in CMT1 patients. Baclofen, naltrexone and sorbitol are shown in green. Red symbols: established or putative functional targets for PTX3003 drugs. Blue arrows: activation links; red lines: inhibition links; dashed lines: functional effect link is receptor-type specific.