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Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease

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Abstract

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy.

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Acknowledgments

The authors’ research is supported by National Institutions of Health (NIH) grants NS063501 (S.M.L.), NS093550 (L.S.C.), GM103613, and NS092343 (L.L.).

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  1. Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Samuel M. Lee

  2. Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Lih-Shen Chin & Lian Li

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Lee, S.M., Chin, LS. & Li, L. Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease. Mol Neurobiol 54, 87–100 (2017). https://doi.org/10.1007/s12035-015-9668-2

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