HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix.
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.
Neuroscience Center, University of Helsinki, Finland.
Mikhail
M
Paveliev
Neuroscience Institute Marseille, France.|Neuroscience and Mental Health Institute, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada.
Keith K
KK
Fenrich
Neuroscience Center, University of Helsinki, Finland.
Mikhail
M
Kislin
Neuroscience Center, University of Helsinki, Finland.
Juha
J
Kuja-Panula
Neuroscience Center, University of Helsinki, Finland.
Evgeny
E
Kulesskiy
Institute of Biotechnology, University of Helsinki, Finland.
Markku
M
Varjosalo
Institute of Biotechnology, University of Helsinki, Finland.
Tommi
T
Kajander
Neuroscience Center, University of Helsinki, Finland.
Ekaterina
E
Mugantseva
Neuroscience Center, University of Helsinki, Finland.
Anni
A
Ahonen-Bishopp
Neuroscience Center, University of Helsinki, Finland.
Leonard
L
Khiroug
Neuroscience Center, University of Helsinki, Finland.
Natalia
N
Kulesskaya
Neuroscience Institute Marseille, France.
Geneviève
G
Rougon
Neuroscience Center, University of Helsinki, Finland.
Heikki
H
Rauvala
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