Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration

Chondroitin sulfate proteoglycans (CSPGs) prevent sympathetic nerve regeneration in the heart after myocardial infarction and prevent central nerve regrowth after traumatic brain injury and spinal cord injury. Currently, there are no small-molecule therapeutics to promote nerve regeneration through CSPG-containing scars. CSPGs bind to monomers of receptor protein tyrosine phosphatase sigma (PTP sigma) on the surface of neurons, enhancing the ability of PTP sigma to bind and dephosphorylate tropomyosin receptor kinases (Trks), inhibiting their activity and preventing axon outgrowth. Targeting PTP sigma-Trk interactions is thus a potential therapeutic target. Here, we describe the development and synthesis of small molecules (HJ-01 and HJ-02) that disrupt PTP sigma interactions with Trks, enhance Trk signaling, and promote sympathetic nerve regeneration over CSPGs.

Automated summary

Chondroitin sulfate proteoglycans (CSPGs) inhibit nerve regeneration, and there is a lack of small-molecule therapeutics to promote nerve growth through CSPG-containing scars. Researchers have developed small molecules that disrupt CSPGs' inhibition of neuron binding and enhance nerve signaling, thus promoting nerve regeneration.