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Brain-Derived Neurotrophic Factor and Rett Syndrome

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Neurotrophic Factors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 220))

Abstract

Rett syndrome (RTT) is a devastating neurodevelopmental disorder with autistic features caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2), a transcriptional regulatory protein. RTT has attracted widespread attention not only because of the urgent need for treatments, but also because it has become a window into basic mechanisms underlying epigenetic regulation of neuronal genes, including BDNF. In addition, work in mouse models of the disease has demonstrated the possibility of symptom reversal upon restoration of normal gene function. This latter finding has resulted in a paradigm shift in RTT research and, indeed, in the field of neurodevelopmental disorders as a whole, and spurred the search for potential therapies for RTT and related syndromes. In this context, the discovery that expression of BDNF is dysregulated in RTT and mouse models of the disease has taken on particular importance. This chapter reviews the still evolving story of how MeCP2 might regulate expression of BDNF, the functional consequences of BDNF deficits in Mecp2 mutant mice, and progress in developing BDNF-targeted therapies for the treatment of RTT.

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Abbreviations

MECP2, BDNF :

Human gene

Mecp2, Bdnf :

Mouse gene

MeCP2, BDNF:

Protein

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Acknowledgments

The author thanks Min Lang and James Cody Howell for help in preparing and reviewing this manuscript and gratefully acknowledges funding support from the National Institutes of Health/National Institute of Neurological Diseases and Stroke, Rett Syndrome Research Foundation, and the International Rett Syndrome Foundation.

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Authors and Affiliations

  1. Department of Neurosciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA

    D. M. Katz

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Correspondence to D. M. Katz .

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Editors and Affiliations

  1. Department of Neuroscience, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Gary R. Lewin

  2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Bruce D. Carter

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Katz, D.M. (2014). Brain-Derived Neurotrophic Factor and Rett Syndrome. In: Lewin, G., Carter, B. (eds) Neurotrophic Factors. Handbook of Experimental Pharmacology, vol 220. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45106-5_18

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