title: Chondroitin sulfate proteoglycans: Key modulators in the developing and pathologic central nervous system.
abstract: Chondroitin Sulfate Proteoglycans (CSPGs) are a major component of the extracellular matrix in the central nervous system (CNS) and play critical role in the development and pathophysiology of the brain and spinal cord. Developmentally, CSPGs provide guidance cues for growth cones and contribute to the formation of neuronal boundaries in the developing CNS. Their presence in perineuronal nets plays a crucial role in the maturation of synapses and closure of critical periods by limiting synaptic plasticity. Following injury to the CNS, CSPGs are dramatically upregulated by reactive glia which form a glial scar around the lesion site. Increased level of CSPGs is a hallmark of all CNS injuries and has been shown to limit axonal plasticity, regeneration, remyelination, and conduction after injury. Additionally, CSPGs create a non-permissive milieu for cell replacement activities by limiting cell migration, survival and differentiation. Mounting evidence is currently shedding light on the potential benefits of manipulating CSPGs in combination with other therapeutic strategies to promote spinal cord repair and regeneration. Moreover, the recent discovery of multiple receptors for CSPGs provides new therapeutic targets for targeted interventions in blocking the inhibitory properties of CSPGs following injury. Here, we will provide an in depth discussion on the impact of CSPGs in normal and pathological CNS. We will also review the recent preclinical therapies that have been developed to target CSPGs in the injured CNS.
authors.affiliation: Regenerative Medicine Program, Department of Physiology and the Spinal Cord Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Dyck
authors.affiliation: Regenerative Medicine Program, Department of Physiology and the Spinal Cord Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: karimis@cc.umanitoba.ca.
authors.forename: Soheila
authors.initials: S
authors.lastname: Karimi-Abdolrezaee
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans
keywords: Axonal regeneration; Central; Chondroitin sulfate proteoglycans; Development; Extracellular matrix; Glial scar; Intacellular mechanisms; LAR; Multiple sclerosis; Nervous system; PTPσ; Plasticity; Spinal cord injury