Myelin-Associated Glycoprotein (MAG)

Myelin-associated glycoprotein (MAG) is a 626-amino acid adhesion molecule that mediates interactions between myelinating cells and neurons through binding to sialic acid-containing gangliosides and neuronal glycoproteins RTN4R and RTN4RL2 (UniProt: P20916). It plays critical roles in maintaining axon myelination, protecting motoneurons from apoptosis, and preventing degeneration of myelinated axons in adults. MAG also functions as a negative regulator of neurite outgrowth, inhibiting axon extension and longitudinal growth through its receptor interactions.

MAG is expressed in myelinating cells and is central to myelin biology and neuronal maintenance. Beyond its physiological role, mutations in MAG are associated with spastic paraplegia 75 (SPG75), an autosomal recessive neurodegenerative disorder characterized by progressive weakness and spasticity of the lower limbs with early childhood onset and mild to moderate cognitive impairment (UniProt: P20916).

In Alzheimer's disease, MAG is down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.394) based on TMT-labeled proteomics analysis across subcellular fractions (Chaparral AD proteomics). The reduction in MAG expression may reflect impaired myelin maintenance and axonal protection mechanisms in AD pathology.