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

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Paveliev , M , Fenrich , K K , Kislin , M , Kuja-Panula , J , Kulesskiy , E , Varjosalo , M , Kajander , T , Mugantseva , E , Ahonen-Bishopp , A , Khirug , L , Kulesskaya , N , Rougon , G & Rauvala , H 2016 , ' HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix ' , Scientific Reports , vol. 6 , 33916 . https://doi.org/10.1038/srep33916

Title: HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix
Author: Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khirug, Leonard; Kulesskaya, Natalia; Rougon, Genevieve; Rauvala, Heikki
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2016-09-27
Language: eng
Number of pages: 17
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/167939
Abstract: 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 PTPs (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.
Subject: SPINAL-CORD-INJURY
GROWTH-ASSOCIATED MOLECULE
CHONDROITIN SULFATE PROTEOGLYCAN
PROMOTES FUNCTIONAL RECOVERY
CENTRAL-NERVOUS-SYSTEM
NEURITE OUTGROWTH
PERINEURONAL NETS
DEVELOPING BRAIN
GLIAL SCAR
PTP-SIGMA
3112 Neurosciences
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