Chondroitin sulfate proteoglycan 5 (CSPG5)

Chondroitin sulfate proteoglycan 5 (CSPG5), also known as Neuroglycan C (NGC) or CALEB, is a brain-specific, type I transmembrane proteoglycan. It belongs to the neuregulin family and contains both chondroitin sulfate glycosaminoglycan side chains and an acidic leucine-rich EGF-like extracellular domain[4][5]. CSPG5 is predominantly expressed in the central nervous system, especially in regions critical for synaptic development such as the hippocampus and cerebellum[2][4]. It plays crucial roles in neural development by regulating neuronal migration, process extension, dendritic branching, and synaptic maturation[2][4][6]. CSPG5 functions, in part, as a growth and differentiation factor involved in neuritogenesis, and can promote neurite outgrowth via the phosphatidylinositol 3-kinase and protein kinase C pathways[4], and by interacting with ErbB3 tyrosine kinase[4][5]. Loss of CSPG5 leads to defective presynaptic development and impaired synapse elimination, contributing to motor coordination impairments[6]. CSPG5 is also implicated in forming extracellular matrix structures (perisynaptic matrices), which modulate synaptic stability and plasticity[2][4]. There are currently no directly interacting drugs, nor is it an established therapeutic biomarker, but CSPG5 and related CSPGs represent targets of interest for overcoming inhibitory extracellular matrix barriers to axon regeneration after central nervous system injury[3]. Note: While frequently referred to as a barrier molecule after injury, CSPG5 itself is more commonly characterized as a developmental and synaptic molecule, with the broad inhibitory effects on axon regeneration after injury more strongly attributed to the CSPG family as a whole[1][3].

Other names

Neuroglycan CCALEBNGCAcidic leucine-rich EGF-like domain-containing brain protein

Drugs targeting CSPG5 would likely modulate neural plasticity, axon regeneration, or synaptic maturation, potentially by antagonizing its inhibitory activity or enhancing neurite outgrowth; supporting evidence on direct drugs is lacking