Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration

Matthew R. Blake, Ryan T. Gardner, Haihong Jin, Melanie A. Staffenson, Nicole J. Rueb, Amy M. Barrios, Gregory B. Dudley, Michael S. Cohen, Beth A. Habecker

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 (PTPσ) on the surface of neurons, enhancing the ability of PTPσ to bind and dephosphorylate tropomyosin receptor kinases (Trks), inhibiting their activity and preventing axon outgrowth. Targeting PTPσ-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 PTPσ interactions with Trks, enhance Trk signaling, and promote sympathetic nerve regeneration over CSPGs.

Original languageEnglish (US)
Pages (from-to)688-699
Number of pages12
JournalACS Chemical Neuroscience
Volume13
Issue number5
DOIs
StatePublished - Mar 2 2022
Externally publishedYes

Keywords

  • acrylamide
  • chondroitin sulfate proteoglycan
  • nerve regeneration
  • protein tyrosine phosphatase receptor sigma

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Fingerprint

Dive into the research topics of 'Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration'. Together they form a unique fingerprint.

Cite this