The small leucine-rich proteoglycans (SLRPs) are a group belonging to the leucine-rich repeat (LRR) superfamily of proteins.

This includes decorin and biglycan (Figure 1C), which have a central region of 10 leucine residues flanked by cysteine residues [73]. Decorin is the best characterized SLRP member and is traditionally associated with ‘decorating’ collagen fibrils. The core protein is 40 kDa and has a single GAG chain attached to a serine residue near the N-terminus. Biglycan is structurally similar, DAPT concentration with a core protein of 45 kDa and two GAG chains. SLRPs evoke a number of signalling pathways and are implicated in multiple interactions including modulation of collagen I and II fibrillogenesis [74]. Decorin expression may have positive effects on repair. It is known to inhibit activity of TGFβ [75] and EGFR [76,77], which have check details regulatory effects on synthesis of inhibitory CSPGs [78,79]. Biglycan also binds TGFβ, and soluble glycosylated biglycan acts as an endogenous ligand of the innate immunity

receptors TLR4 and TLR2 in macrophages (reviewed in [80]). Thus, the CSPGs comprise a complex family of molecules that are key components of the ECM. The multiple interactions of CSPGs with other ECM molecules as well as their binding affinity for a diverse array of growth factors, cytokines and receptors all suggest that they are crucial players in the CNS response to injury and that ECM modification will be an important therapeutic target. In addition to specific targeting of individual CSPGs (such as the function blocking NG2 antibody), global targeting of CSPGs has been a widely used strategy in experimental studies, for example by enzymatic digestion of CS-GAG chains to reduce the growth inhibitory properties of CSPGs. These approaches will be discussed

in detail later in this review. Many of the above ECM molecules have been targeted in repair strategies, often in an attempt to recapitulate developmental processes, where they play an important role in cell proliferation, migration, axon guidance and plasticity. Below we will discuss some of these PD184352 (CI-1040) processes. Correct wiring of the nervous system requires the precise distribution and connectivity of millions of cells during development. The ECM plays a key role, conferring many of the properties required to form intricate networks with specificity and reliability. During embryogenesis, neural induction and neural tube formation are followed by rapid cell proliferation, migration and differentiation of cells to neurones and glia to form the CNS. Subsequent to regionalization of neurones, connections form between them. Connections form when a differentiated neurone sends out an axon, tipped by a growth cone which responds to multiple sources of extracellular cues to reach its target.