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Gαq takes centre stage in multiple sclerosis pathogenesis

Cellular & Molecular Immunology volume 14, pages 401–402 (2017)Cite this article

There is no cure for multiple sclerosis (MS); however, a number of strategies exist for disease management, including medications that reduce the frequency of relapses and long-term accrual of disability.1 However, the fact that MS therapies can be partially effective and have the risk of side effects, in addition to the observation that disability often continues to worsen despite immunotherapy, has highlighted the need for novel therapeutic targets in the disease.

Heterotrimeric G proteins mediate a diverse array of physiological responses to extracellular stimuli (neurotransmitters, chemokines, hormones and environmental stimuli) received by G protein-coupled receptors (GPCRs).2 GPCRs are important drug targets in human disease,3 and more importantly, dysfunction of genes encoding G proteins is linked to certain diseases in humans, including inflammation, cancer and neurological disorders.4 In particular, considerable evidence indicates that GPCRs mediate key processes underpinning the development of MS and experimental autoimmune encephalomyelitis (EAE), including blood−brain barrier permeability, T-cell activation, antigen presentation and glial reactivity.3 Indeed, fingolimod (Gilenya, Novartis, Switzerland), the currently available immunomodulatory therapy for MS, targets the sphingosine-1 phosphate (S1P) receptor, a ubiquitous GPCR.5 Activation of this GPCR results in the prevention of lymphocyte egress from lymph nodes,6 thus reducing infiltration into the central nervous system and immune-mediated cellular damage in MS.

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  1. School of Medicine, Discipline of Physiology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, 2, Ireland

    Eric J Downer

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Correspondence to Eric J Downer.

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Downer, E. Gαq takes centre stage in multiple sclerosis pathogenesis. Cell Mol Immunol 14, 401–402 (2017). https://doi.org/10.1038/cmi.2017.6

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