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Endoplasmic reticulum stress in disorders of myelinating cells

Nature Neuroscience volume 12, pages 379–385 (2009)Cite this article

Abstract

Myelinating cells, oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system produce an enormous amount of plasma membrane during the myelination process, making them particularly susceptible to disruptions of the secretory pathway. Endoplasmic reticulum stress, initiated by the accumulation of unfolded or misfolded proteins, activates the unfolded protein response, which adapts cells to the stress. If this adaptive response is insufficient, the unfolded protein response activates an apoptotic program to eliminate the affected cells. Recent observations suggest that endoplasmic reticulum stress in myelinating cells is important in the pathogenesis of various disorders of myelin, including Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher disease and Vanishing White Matter Disease, as well as in the most common myelin disorder, multiple sclerosis. A better understanding of endoplasmic reticulum stress in myelinating cells has laid the groundwork for the design of new therapeutic strategies for promoting myelinating cell survival in these disorders.

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Figure 1: Oligodendrocyte and myelin.
Figure 2: The UPR pathway in eukaryotic cells.

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Acknowledgements

We thank D. Douglas for critical comments on the manuscript. W.L. is supported by a National Multiple Sclerosis Society Career Transition Fellowship grant (TA 3026-A-1). B.P. is supported by grants from the US National Institutes of Health (NS34939 and 027336) and the Myelin Repair Foundation.

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  1. Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, Alabama, USA

    Wensheng Lin

  2. Department of Neurology, The Jack Miller Center for Peripheral Neuropathy, The University of Chicago, Chicago, Illinois, USA

    Brian Popko

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Lin, W., Popko, B. Endoplasmic reticulum stress in disorders of myelinating cells. Nat Neurosci 12, 379–385 (2009). https://doi.org/10.1038/nn.2273

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