Blocking LINGO1 in fish promotes myelination

Yin W, Hu B Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish. Exp Neurol. 2013 Nov. doi:pii: S0014-4886(13)00336-1.10.1016/j.expneurol.2013.11.012. [Epub ahead of print]

Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) has been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development.
The Zebrafish has clear young and you can genetically manipulate the fish so you can see myelination happening. In this study they look at the effect of blocking LINGO1 and this caused more myelin to form and also helped nerves grow,so if it is important in myelin formation in fish and rodents, there is a good chance it is important in humans too. Pharma thinks so and there are studies to deliver a LINGO-1 blocking molecule. I only hope enough of it can get into the CNS to do its stuff.

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