Mag, also known as myelin-associated glycoprotein (MAG) and SIGLEC-4, is a member of the siglec family. It binds preferentially to sialic acids α(2-3)-linked to D-galactose. MAG is involved in axon stability and regeneration through interactions with sialylated gangliosides [1]. It is expressed by Schwann cells and oligodendrocytes and plays a role in maintaining myelin integrity, inhibiting axonal regeneration from cerebellar neurons in the central nervous system, and mediating adhesion between the Schwann cell membrane and axons in the peripheral nervous system [4].

In a study on cerebellar granule neurons (CGNs), it was found that MAG expression in the cerebellum is compartmentalized, with higher levels in the white matter. MAG induces apoptosis in developing CGNs through p75NTR signalling, and deletion of p75NTR in vivo reduced the number of apoptotic neurons in the cerebellar white matter during development, leading to a reduction in the size of the white matter in adulthood. MAG also impairs CGNs neurite outgrowth as a consequence of apoptosis [3].

In conclusion, Mag is crucial for processes related to myelin integrity, axon stability, and regeneration. Studies using in vivo models, such as the deletion of p75NTR in relation to MAG-induced apoptosis in CGNs, have revealed its role in cerebellar development. Additionally, Mag is associated with various neuropathies, like anti-MAG neuropathy, where changes in anti-MAG autoantibodies are related to therapy response, highlighting its importance in understanding and treating these diseases [2].

References:

1. Schwardt, Oliver, Kelm, Soerge, Ernst, Beat. . SIGLEC-4 (MAG) Antagonists: From the Natural Carbohydrate Epitope to Glycomimetics. In Topics in current chemistry, 367, 151-200. doi:10.1007/128_2013_498. https://pubmed.ncbi.nlm.nih.gov/24276958/

2. Hänggi, Pascal, Aliu, Butrint, Martin, Kea, Herrendorff, Ruben, Steck, Andreas Johann. 2021. Decrease in Serum Anti-MAG Autoantibodies Is Associated With Therapy Response in Patients With Anti-MAG Neuropathy: Retrospective Study. In Neurology(R) neuroimmunology & neuroinflammation, 9, . doi:10.1212/NXI.0000000000001109. https://pubmed.ncbi.nlm.nih.gov/34759022/

3. Fernández-Suárez, Diana, Krapacher, Favio A, Andersson, Annika, Ibáñez, Carlos F, Kisiswa, Lilian. 2019. MAG induces apoptosis in cerebellar granule neurons through p75NTR demarcating granule layer/white matter boundary. In Cell death & disease, 10, 732. doi:10.1038/s41419-019-1970-x. https://pubmed.ncbi.nlm.nih.gov/31570696/

4. Zis, Panagiotis, Rao, Dasappaiah Ganesh, Hoggard, Nigel, Sarrigiannis, Ptolemaios Georgios, Hadjivassiliou, Marios. 2017. Anti-MAG associated cerebellar ataxia and response to rituximab. In Journal of neurology, 265, 115-118. doi:10.1007/s00415-017-8675-9. https://pubmed.ncbi.nlm.nih.gov/29159464/