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Inhibitors of Myelination and Remyelination, Bone Morphogenetic Proteins, are Upregulated in Human Neurological Disease

Abstract

During demyelinating disease such as multiple sclerosis and stroke, myelin is destroyed and along with it, the oligodendrocytes that synthesize the myelin. Thus, recovery is limited due to both interruptions in neuronal transmission as well as lack of support for neurons. Although oligodendrocyte progenitor cells remain abundant in the central nervous system, they rarely mature and form new functional myelin in the diseased CNS. In cell culture and in experimental models of demyelinating disease, inhibitory signaling factors decrease myelination and remyelination. One of the most potent of these are the bone morphogenetic proteins (BMPs), a family of proteins that strongly inhibits oligodendrocyte progenitor differentiation and myelination in culture. BMPs are highly expressed in the dorsal CNS during pre-natal development and serve to regulate dorsal ventral patterning. Their expression decreases after birth but is significantly increased in rodent demyelination models such as experimental autoimmune encephalomyelitis, cuprizone ingestion and spinal cord injury. However, until recently, evidence for BMP upregulation in human disease has been scarce. This review discusses new human studies showing that in multiple sclerosis and other demyelinating diseases, BMPs are expressed by immune cells invading the CNS as well as resident CNS cell types, mostly astrocytes and microglia. Expression of endogenous BMP antagonists is also regulated. Identification of BMPs in the CNS is correlated with areas of demyelination and inflammation. These studies further support BMP as a potential therapeutic target.

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Acknowledgements

This project was supported by the following Grant: National MS Society RG1506-04717

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Correspondence to Judith B. Grinspan.

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Grinspan, J.B. Inhibitors of Myelination and Remyelination, Bone Morphogenetic Proteins, are Upregulated in Human Neurological Disease. Neurochem Res (2020). https://doi.org/10.1007/s11064-020-02980-w

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Keywords

  • Bone morphogenetic proteins
  • Oligodendrocytes
  • Demyelination
  • Remyelination
  • Smads
  • Inhibitory signaling factors