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The functions of mTOR complex subunits Rictor and Raptor in myelination

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New insight into demyelination

Dissecting the basic principles of myelination has important ramifications for clinical neuroscience. With this in mind, a European study concentrated on the role of the mammalian target of rapamycin (mTOR) pathway in myelin production.


Central to proper neuronal signal transmission is the myelination of axons. This acts as an insulator while maintaining signal strength during signal propagation. In disorders such as multiple sclerosis, the loss of the myelin sheath has devastating consequences in the normal function of the nervous system. Understanding the molecular processes responsible for myelination could provide future therapeutic solutions for demyelinating conditions. In this context, scientists on the EU-funded 'The functions of mTOR complex subunits Rictor and Raptor in myelination' (MTORC IN MYELINATION) project were interested in the role of the mTOR pathway. mTOR signalling is a central regulator of cell growth and metabolism, and is intimately linked with PI3K-Akt signalling. The latter pathway seems to be involved in regulating myelin production through Schwann cells and subsequent coating of neurons. MTORC IN MYELINATION members focused on the role of mTOR signalling in the peripheral nervous system. To this end, researchers deleted the subunits Raptor and Rictor in the two mTOR complexes mTORC1 and mTORC2, respectively. They then assessed the effects of deletion on myelin production in Schwann cells. They also analysed nerves from transgenic knockout mice at different time points of development to delineate the induced morphological and biochemical alterations. The nerves lacking Raptor exhibited impaired myelination, both during development and in regeneration after injury. Signalling pathways downstream of mTOR were also severely affected, resulting in defective myelin production. The data generated during the study underscore the importance of the mTOR pathway in functional myelin production and provide novel targets for therapeutic intervention. Pharmacological activation of mTOR which is being explored elsewhere could also find application for the treatment of demyelinating disorders.


Myelination, mTOR, multiple sclerosis, Rictor, Raptor, Schwann cell, neurons

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