engleski

Myelin-Associated Glycoprotein (Siglec-4) in Axon Regeneration

Myelin-associated glycoprotein (MAG), a member of the Siglec (sialic acid-binding immunoglobulin-like lectin) family, is expressed on myelin that surrounds axons throughout the nervous system. MAG on the inner-most myelin wrap (apposed to the axon) enhances axon stability. However, after injury (e.g. spinal cord injury) MAG on residual myelin inhibits axon regeneration. Blocking MAG’ s inhibitory signals may allow axons to regenerate and enhance functional recovery. MAG inhibition of axon regeneration is mediated, in part, by its binding to sialoglycans on the axon. Spinal cord injury models were used to test whether disruption of MAG-sialoglycan binding enhances recovery. In brachial plexus avulsion injury the nerves that connect the arm to the spinal cord are violently yanked out. Nerve grafts have been used to bridge the spinal cord back to the remaining nerve stump, but poor axon outgrowth hampered functional recovery. We cut the brachial plexus of rats and inserted a nerve graft into the spinal cord at the injury site. Delivery of bacterial sialidase to disrupt MAG-sialoglycan binding enhanced spinal axon outgrowth into the graft 2.5-fold. In a second model, rats were subjected to blunt contusion spinal cord injury. Delivery of bacterial sialidase to the injury site significantly enhanced motor behaviour and autonomic control of blood pressure, two measures of functional recovery. Together these data support the conclusion that sialic acid-directed therapies might contribute to anatomical and functional recovery of the injured spinal cord.

gangliosides; myelin- associated glycoprotein; axon regeneration

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