期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 52, 期 -, 页码 12-20出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2016.01.040
关键词
mTOR; Neuronal differentiation; Neuronal migration; Epilepsy; TSC; Neural stem cell
资金
- Canadian Institutes of Health Research [201503MOP-342469]
- European Union Programme of the Seventh Framework Programme Development of Strategies for Innovative Research [602531]
- Waterloo Foundation
- Charles Sykes Epilepsy Research Trust
- NIHR Specialist Biomedical Research Centre for Mental Health of South London and Maudsley NHS Foundation Trust
Understanding the development and function of the nervous system is one of the foremost aims of current biomedical research. The nervous system is generated during a relatively short period of intense neurogenesis that is orchestrated by a number of key molecular signalling pathways. Even subtle defects in the activity of these molecules can have serious repercussions resulting in neurological, neurodevelopmental and neurocognitive problems including epilepsy, intellectual disability and autism. Tuberous sclerosis complex (TSC) is a monogenic disease characterised by these problems and by the formation of benign tumours in multiple organs, including the brain. TSC is caused by mutations in the TSC1 or TSC2 gene leading to activation of the mechanistic target of rapamycin (mTOR) signalling pathway. A desire to understand the neurological manifestations of TSC has stimulated research into the role of the mTOR pathway in neurogenesis. In this review we describe TSC neurobiology and how the use of animal model systems has provided insights into the roles of mTOR signalling in neuronal differentiation and migration. Recent progress in this field has identified novel mTOR pathway components regulating neuronal differentiation. The roles of mTOR signalling and aberrant neurogenesis in epilepsy are also discussed. Continuing efforts to understand mTOR neurobiology will help to identify new therapeutic targets for TSC and other neurological diseases. (C) 2016 Elsevier Ltd. All rights reserved.
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