Nogo and the Nogo-66 receptor.
Nogo has been identified as a component of central nervous system (CNS) myelin preventing axonal regeneration in the adult vertebrate CNS. Our previous analysis of Nogo-A demonstrated that an axon-inhibiting 66 aa domain is expressed at the extracellular surface and the endoplasmic reticulum lumen of transfected cells and oligodendrocytes. We have identified a brain-specific, leucine-rich repeat protein with high affinity for soluble Nogo-66. Cleavage of the Nogo-66 receptor from axonal surfaces renders neurons insensitive to Nogo-66. Nogo-66 receptor expression is sufficient to impart Nogo-66 axonal inhibition to unresponsive neurons. With identified ligand and receptor components, structure-function determinants for inhibition of axon regeneration can now be mapped. The relative contribution of Nogo, myelin-associated glycoprotein, chondroitin sulfate proteoglycan and oligodendrocyte myelin glycoprotein to myelin inhibition can be assessed. Blockade of Nogo-66 interaction with its receptor provides one potential avenue to promote axonal regeneration after adult mammalian CNS injury.[1]References
- Nogo and the Nogo-66 receptor. Fournier, A.E., GrandPré, T., Gould, G., Wang, X., Strittmatter, S.M. Prog. Brain Res. (2002) [Pubmed]
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