Modulation of the proteoglycan receptor PTPσ induces neuronal protease release to overcome Chondroitin Sulfate Proteoglycan inhibition of axon regeneration

Over the next few weeks I’ll post just a few of the interesting poster abstracts from the Society for Neuroscience conference held in Chicago this year. There’s too many to include them all, however, you’ll get a feel for where the research is at by reading through some of these highlights.

Society for Neuroscience Chicago 2015

Poster 066. Spinal Cord Injury: Neuroplasticity Location: Hall A Time: Saturday, October 17, 2015, 1:00 PM – 5:00 PM Program#/Poster#: 66.09/N14
Topic: D.10. Spinal Cord Injury and Plasticity
Support: NIH-NS 025713
Case Western Reserve University Council to Advance Human Health
Unite to Fight Paralysis
Spinal Cord Injury Sucks

Title: Modulation of the proteoglycan receptor PTPσ induces neuronal protease release to overcome Chondroitin Sulfate Proteoglycan inhibition of axon regeneration

Authors: *A. TRAN1, B. T. LANG2, J. SILVER1; 1Neurosciences, Case Western Reserve Univ., Cleveland, OH; 2Athersys, Cleveland, OH

Abstract: Following spinal cord injury, newly reformed growth cones of regenerating axons are halted by the extracellular matrix (ECM) of the glial scar. One ECM component in particular, chondroitin sulfate proteoglycans (CSPGs), actively prevent regeneration and sprouting through increased expression in both the lesion scar and perineuronal nets surrounding deafferented neurons. Protein Tyrosine Phosphatase-Sigma (PTPσ) has been identified as a receptor for CSPGs that is sufficient to signal axonal growth inhibition. Further, manipulation of PTPσ with the novel Intracellular Sigma Peptide (ISP), unlocks axonal plasticity within CSPG rich regions through a currently unknown molecular mechanism. We previously demonstrated that ISP treatment enhances recovery of sensorimotor, locomotor, and urinary function following severe spinal cord injury via unprecedented serotonergic sprouting (Lang et al. 2015). We now report that modulation of PTPσ, both in vivo and in vitro, increases the release of protease(s) from neurons that digest inhibitory components of the ECM, such as aggrecan. Using gel zymography, western blots, and in vitro assays, we were able to demonstrate that ISP induced protease digestion of aggrecan. Thus, we hypothesize that one of the critical downstream events underlying the failure of axon regeneration is a lack of cell growth-permitting protease release within CSPG rich regions. Further understanding of the mechanisms underlying CSPG-PTPσ signaling will further elucidate how axon regeneration is impaired following spinal cord injury.

Disclosures: A. Tran: None. B.T. Lang: A. Employment/Salary (full or part-time):; Athersys, Inc.. J. Silver: None.

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