Nogo BACE jumps on the exosome

Abstract

The protein Nogo-A has been widely studied for its role in inhibiting axonal regeneration following injury to the central nervous system, but the mechanism by which the membrane-bound Nogo-A is presented intercellularly is not fully understood. New research suggests that a highly inhibitory fragment of Nogo-A is generated by the amyloid precursor protein protease BACE1 and presented on the membranes of exosomes following spinal cord injury. This finding represents a new mode through which Nogo-A may exert its effects in the central nervous system.

Figure 1.

Illustration of how exosomal Nogo-24 may be released after spinal cord injury and signal through NgR1 to inhibit neuron regeneration. 1, BACE1 cleaves full-length Nogo-A to Nogo-24. Nogo-24–containing exosomes are produced in the endosomal pathway and released when the multivesicular body fuses with the plasma membrane. 2, exosomes reach the neuronal plasma membrane, where Nogo-24 can interact with NgR1 and its coreceptors. 3, Nogo-24 binding to NgR1 is transduced through a co-receptor to NgR1 and leads to downstream signaling inhibiting axonal regeneration and sprouting.