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The chondroitin sulfate proteoglycans (CSPGs) are large groups of heterogenous proteoglycans that are mainly expressed by reactive astrocytes in the central nervous system (CNS). They share similar core proteins and are post-transcriptionally modified by chondroitin sulfate glycosaminoglycans. CSPGs are the major components of the perineuronal nets (PNN) that regulate the opening and closure of the critical period. Mounting reports have documented the crucial roles of CSPGs in restricting neuronal plasticity, axonal growth, and pathfinding during development as well as axonal regeneration after CNS injury. Moreover, CSPGs and PNNs modulate long-term memory, which impairments frequently happened in several neurodegenerative and psychiatric disorders. This review will shortly introduce the expression patterns of CSPGs during development and after injury, the PNNs constitutions, the roles of CSPGs and PNNs in axonal regrowth, discuss the most recently identified roles of CSPGs and PNNs in mediating long-term memory and their correlation with brain disorders, and finally, propose a short perspective of future investigations. Hopefully, further explorations may validate the therapeutic potentials of PNNs and CSPGs.

Chondroitin sulfate proteoglycans: key modulators of neuronal plasticity, long-term memory, neurodegenerative, and psychiatric disorders