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HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix.

Authors: Paveliev, Mikhail  Fenrich, Keith K  Kislin, Mikhail  Kuja-Panula, Juha  Kulesskiy, Evgeny  Varjosalo, Markku  Kajander, Tommi  Mugantseva, Ekaterina  Ahonen-Bishopp, Anni  Khiroug, Leonard  Kulesskaya, Natalia  Rougon, Geneviève  Rauvala, Heikki 
Citation: Paveliev M, etal., Sci Rep. 2016 Sep 27;6:33916. doi: 10.1038/srep33916.
Pubmed: (View Article at PubMed) PMID:27671118
DOI: Full-text: DOI:10.1038/srep33916

Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries.


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CRRD Object Information
CRRD ID: 14397577
Created: 2019-04-10
Species: All species
Last Modified: 2019-04-10
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.