Small Molecules Targeting PTPσ–Trk Interactions Promote Sympathetic Nerve Regeneration
Open Access
- 14 February 2022
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Chemical Neuroscience
- Vol. 13 (5) , 688-699
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.Keywords
Funding Information
- M.J. Murdock Charitable Trust
- Oregon Health and Science University
- National Heart, Lung, and Blood Institute (F31HL152490, R01 HL093056)
- American Heart Association (19POST34460031, 20PRE35210768)
- Oregon Clinical and Translational Research Institute
- National Institute of General Medical Sciences (GM135295, P20GM103434)
- Morton Cure Paralysis Fund
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