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CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury

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Abstract

Neurodegeneration in the adult mammalian central nervous system (CNS) is fundamentally accelerated by its intrinsic neuronal mechanisms, including its poor regenerative capacity and potent extrinsic inhibitory factors. Thus, the treatment of neurodegenerative diseases faces many obstacles. The degenerative processes, consisting of axonal/dendritic structural disruption, abnormal axonal transport, release of extracellular factors, and inflammation, are often controlled by the cytoskeleton. From this perspective, regulators of the cytoskeleton could potentially be a therapeutic target for neurodegenerative diseases and CNS injury. Collapsin response mediator proteins (CRMPs) are known to regulate the assembly of cytoskeletal proteins in neurons, as well as control axonal growth and neural circuit formation. Recent studies have provided some novel insights into the roles of CRMPs in several inhibitory signaling pathways of neurodegeneration, in addition to its functions in neurological disorders and CNS repair. Here, we summarize the roles of CRMPs in axon regeneration and its emerging functions in non-neuronal cells, especially in inflammatory responses. We also discuss the direct and indirect targeting of CRMPs as a novel therapeutic strategy for neurological diseases.

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Acknowledgments

We would like to thank Dr. Yoshio Goshima from the Department of Molecular Pharmacology and Neurobiology at Yokohama City University for his collaboration. We apologize to the authors whose relevant work we could not cite due to space limitations.

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Authors and Affiliations

  1. Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu-cho Shinjuku-ku, Tokyo, 162-8480, Japan

    Jun Nagai, Rina Baba & Toshio Ohshima

  2. Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan

    Jun Nagai

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  1. Jun Nagai
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  2. Rina Baba
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  3. Toshio Ohshima
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Correspondence to Toshio Ohshima.

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This work was supported by grants from Grant-in-Aid for JSPS Fellows (J.N.), JSPS KAKENHI Grant Number 26430043 (T.O.) and Waseda University Grant for Special Research Projects (2013B-171 to T.O.). The authors declare no competing financial interests.

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Nagai, J., Baba, R. & Ohshima, T. CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury. Mol Neurobiol 54, 4243–4256 (2017). https://doi.org/10.1007/s12035-016-0005-1

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