Neuronal Axon Generation/Regeneration Regulated by Sulfated Glycans

It has long been recognized that central nerve axons do not regenerate spontaneously in adults. On the other hand, it is also known that axons of embryonic neurons and peripheral neurons, even of adults, can regenerate and reconstruct neural circuits. These differences can be attributed to intrinsic factors, that is, the regenerative capacities of neurons, and extrinsic factors, that is, the extracellular environments. Recent analyses at the single-cell level have led to a better understanding of the molecular mechanisms that underlie differences in the regenerative ability of neurons. At the same time, our understanding of the extracellular environments that determine whether neural axons can regenerate has also advanced. Sulfated glycans, which are sugar chains known as "third life chains" in addition to nucleic acids and proteins, are among the most important extracellular molecules involved in conferring regenerative capacity. Once thought to be merely a physical barrier to neuronal axons, the sulfated glycans have recently been shown to inhibit neuronal axon regeneration via their specific neuronal receptors and intracellular signaling. In this chapter, we will introduce the recent advances in our understanding of the regulation of nerve axons by sulfated glycans, while unraveling the history of research on axon regeneration.