PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration

Rajeev Sivasankaran, Jiong Pei, Kevin C. Wang, Yi Ping Zhang, Christopher B. Shields, Xiao-Ming Xu, Zhigang He

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

Successful axon regeneration in the mammalian central nervous system (CNS) is at least partially compromised due to the inhibitors associated with myelin and glial scar. However, the intracellular signaling mechanisms underlying these inhibitory activities are largely unknown. Here we provide biochemical and functional evidence that conventional isoforms of protein kinase C (PKC) are key components in the signaling pathways that mediate the inhibitory activities of myelin components and chondroitin sulfate proteoglycans (CSPGs), the major class of inhibitors in the glial scar. Both the myelin inhibitors and CSPGs induce PKC activation. Blocking PKC activity pharmacologically and genetically attenuates the ability of CNS myelin and CSPGs to activate Rho and inhibit neurite outgrowth. Intrathecal infusion of a PKC inhibitor, Gö6976, into the site of dorsal hemisection promotes regeneration of dorsal column axons across and beyond the lesion site in adult rats. Thus, perturbing PKC activity could represent a therapeutic approach to stimulating axon regeneration after brain and spinal cord injuries.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalNature Neuroscience
Volume7
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

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Chondroitin Sulfate Proteoglycans
Myelin Sheath
Protein Kinase C
Regeneration
Axons
Neuroglia
Cicatrix
Central Nervous System
Protein C Inhibitor
Protein Kinase Inhibitors
Spinal Cord Injuries
Protein Isoforms
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

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PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. / Sivasankaran, Rajeev; Pei, Jiong; Wang, Kevin C.; Zhang, Yi Ping; Shields, Christopher B.; Xu, Xiao-Ming; He, Zhigang.

In: Nature Neuroscience, Vol. 7, No. 3, 03.2004, p. 261-268.

Research output: Contribution to journalArticle

Sivasankaran, Rajeev ; Pei, Jiong ; Wang, Kevin C. ; Zhang, Yi Ping ; Shields, Christopher B. ; Xu, Xiao-Ming ; He, Zhigang. / PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. In: Nature Neuroscience. 2004 ; Vol. 7, No. 3. pp. 261-268.
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