2005 年 33 巻 6 号 p. 395-397
Axons of the adult central nervous system are capable of only limited regrowth after injury, and an unfavorable environment plays a major role in the lack of regeneration. Some of the axon growth inhibitory effects are associated with myelin. Identification of the myelin-derived inhibitors has led to a spurt in our knowledge about the molecular mechanisms.
The neurotrophin receptor p75, which has long been known as a receptor for neurotrophins that promote survival and differentiation, transduces the signal from all of the myelin-derived inhibitors found to date. p75NTR has the ability to elicit bi-directional signals, which result in the inhibition as well as the promotion of the neurite outgrowth. p75NTR, in response to myelin-derived inhibitors, elicits activation of Rho, one of the key regulators of actin cytoskeleton. Activation of Rho is required for axon growth inhibition in vitro as well as in vivo.
These findings establish Rho as a key player in inhibiting the regeneration of the central nervous system, and launched a new wave of studies aimed at promoting regeneration of injured axons by modulating this inhibitory pathway.