Author(s): Fournier AE, GrandPr T, Gould G, Wang X, Strittmatter SM
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Abstract 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.
This article was published in Prog Brain Res
and referenced in Journal of Addiction Research & Therapy