Multiple signals regulate axon regeneration through the Nogo receptor complex.
Several myelin-derived proteins have been identified as components of central nervous system (CNS) myelin, which prevents axonal regeneration in the adult vertebrate CNS. The discovery of the receptor for these proteins was a major step toward understanding the failure of axon regeneration. The receptor complex consists of at least three elements: the p75 receptor (p75NTR), the Nogo receptor and LINGO-1. Downstream from the receptor complex, RhoA activation has been shown to be a key element of the signaling mechanism of these proteins. Rho activation arrests axon growth, and blocking Rho activation promotes axon regeneration in vivo. Recent studies have identified conventional protein kinase C as an additional necessary component for axon growth inhibition. Possible crosstalk downstream of these signals should be explored to clarify all the inhibitory signals and may provide an efficient molecular target against injuries to the CNS.
Yamashita
Toshihide
T
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. t-yamashita@faculty.chiba-u.jp
Fujitani
Masashi
M
Yamagishi
Satoru
S
Hata
Katsuhiko
K
Mimura
Fumiaki
F
D000818:Animals; D001369:Axons / Q000378:metabolism*; D006801:Humans; D009185:Myelin Proteins / Q000378:metabolism*; D009416:Nerve Regeneration; D000070798:Nogo Proteins; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; D011493:Protein Kinase C; D020741:rho GTP-Binding Proteins