The adult central nervous system (CNS) has limited capacity for axon regeneration after injury, primarily due to the inhibitory environment created by glial cells. This environment includes inhibitory molecules in myelin and proteoglycans from astroglial scarring. The molecular basis of these inhibitory influences and their roles in limiting axon repair and structural plasticity are discussed. Understanding these mechanisms is crucial for developing therapies to promote functional recovery after neural injury. The CNS has the ability to adapt and respond to various stimuli, including structural remodeling. However, axons in the adult CNS fail to regenerate beyond the injury site, unlike those in the peripheral nervous system (PNS) or embryonic nervous system. Recent evidence suggests that some molecular mechanisms involved in structural plasticity, including short-range remodelling and long-distance axon regrowth, are similar. Targeting these mechanisms could promote axon regeneration and enhance plasticity after CNS injury. The glial environment of the adult CNS is different from the PNS or embryonic nervous system. Myelin, which normally protects axons, can become damaged after injury, exposing axons to myelin-associated inhibitors. Reactive astrocytes form a glial scar at the injury site, which may act as an additional barrier to axon regrowth. Myelin-associated inhibitors include Nogo-A, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and transmembrane semaphorin 4D (Sema4D/CD100). These molecules inhibit axon outgrowth and are expressed by both CNS oligodendrocytes and PNS Schwann cells. CSPGs, a family of inhibitory extracellular matrix molecules, are also involved in axon regeneration failure. They are released by reactive astrocytes after injury and form an inhibitory gradient at the injury site. CSPGs can be neutralized by chondroitinase ABC (ChABC), which removes GAG chains from the protein core. However, the mechanisms by which CSPGs exert their inhibitory effects are still not fully understood. The Nogo-66 receptor (NgR) is a GPI-linked protein that interacts with Nogo-A, MAG, and OMgp. Other co-receptors, such as p75 and TROY, also play a role in mediating myelin inhibition. The intracellular signaling pathways triggered by myelin-associated inhibitors include RhoA and its effector, ROCK. These pathways are involved in the regulation of the actin cytoskeleton and the stability of the growth cone. In vivo studies have shown that targeting inhibitory signals can promote axon regeneration and functional recovery after CNS injury. However, the success of these approaches varies, and the relative contributions of different inhibitory factors remain unclear. The glial scar and myelin-associated inhibitors are both involved in regenerative failure, with some overlap in theirThe adult central nervous system (CNS) has limited capacity for axon regeneration after injury, primarily due to the inhibitory environment created by glial cells. This environment includes inhibitory molecules in myelin and proteoglycans from astroglial scarring. The molecular basis of these inhibitory influences and their roles in limiting axon repair and structural plasticity are discussed. Understanding these mechanisms is crucial for developing therapies to promote functional recovery after neural injury. The CNS has the ability to adapt and respond to various stimuli, including structural remodeling. However, axons in the adult CNS fail to regenerate beyond the injury site, unlike those in the peripheral nervous system (PNS) or embryonic nervous system. Recent evidence suggests that some molecular mechanisms involved in structural plasticity, including short-range remodelling and long-distance axon regrowth, are similar. Targeting these mechanisms could promote axon regeneration and enhance plasticity after CNS injury. The glial environment of the adult CNS is different from the PNS or embryonic nervous system. Myelin, which normally protects axons, can become damaged after injury, exposing axons to myelin-associated inhibitors. Reactive astrocytes form a glial scar at the injury site, which may act as an additional barrier to axon regrowth. Myelin-associated inhibitors include Nogo-A, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and transmembrane semaphorin 4D (Sema4D/CD100). These molecules inhibit axon outgrowth and are expressed by both CNS oligodendrocytes and PNS Schwann cells. CSPGs, a family of inhibitory extracellular matrix molecules, are also involved in axon regeneration failure. They are released by reactive astrocytes after injury and form an inhibitory gradient at the injury site. CSPGs can be neutralized by chondroitinase ABC (ChABC), which removes GAG chains from the protein core. However, the mechanisms by which CSPGs exert their inhibitory effects are still not fully understood. The Nogo-66 receptor (NgR) is a GPI-linked protein that interacts with Nogo-A, MAG, and OMgp. Other co-receptors, such as p75 and TROY, also play a role in mediating myelin inhibition. The intracellular signaling pathways triggered by myelin-associated inhibitors include RhoA and its effector, ROCK. These pathways are involved in the regulation of the actin cytoskeleton and the stability of the growth cone. In vivo studies have shown that targeting inhibitory signals can promote axon regeneration and functional recovery after CNS injury. However, the success of these approaches varies, and the relative contributions of different inhibitory factors remain unclear. The glial scar and myelin-associated inhibitors are both involved in regenerative failure, with some overlap in their