Chondroitin Sulfates in Axon Regeneration and Plasticity

Abstract

Chondroitin sulfate proteoglycans (CSPGs) are large extracellular matrix molecules which are highly upregulated in the glial scar after injury to the nervous system. They are mostly inhibitory and have been shown to hinder regeneration of axons across lesions. The removal of CPSGs with bacterial enzyme chondroitinase ABC improves axonal regeneration. In addition, CSPGs are a major component of perineuronal nets, which control plasticity in the CNS, and their removal enhances structural plasticity resulting in an increase in functional recovery. In this review, we shall discuss the role of CSPGs in axonal regeneration and plasticity after nervous system injury and how recent discoveries of CSPG receptors and interacting partners may shed new insights onto the function of these inhibitory molecules. A. IntroductionThe extension of axons during growth and regeneration is dependent on the various extracellular matrix (ECM) molecules present in the surrounding environment (1). These molecules can be growth-promoting, e.g. laminin, fibronectin and collagen; or growth-inhibitory, e.g. CSPGs and tenascin. The relative balance of promoting and inhibitory factors together with the properties of the axons determines their growth and guidance. The strong upregulation of CSPGs at the site of injury hampers the endogenous regeneration abilities of neurons. Here, we are going to examine the role of CSPGs after injury, the use of chondroitinase ABC (ChABC) in promoting regeneration and plasticity and recent advances towards understanding the mechanism of CSPG inhibition. B. CSPGs on Regeneration and Plasticity after Nervous System InjuryThe ECM of the central nervous system (CNS) is unique in its composition and organization with relatively small quantities of fibrous structural proteins and high levels

The Extracellular Matrix in the Nervous System: The Good and the Bad Aspects

“…CSPGs in the CNS also aggregate into a macromolecular structure on the surface of neurons called perineuronal nets (PNNs) [33,34]. PNNs are dense matrix structures formed by four families of brain ECM molecules, including CSPGs, hyaluronan, hyaluronan, and proteoglycan link proteins (HAPLNs) and tenascins [33].…”