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Acta Neuropathologica

, Volume 137, Issue 4, pp 535–555 | Cite as

Translational control in brain pathologies: biological significance and therapeutic opportunities

  • Alberto DelaidelliEmail author
  • Asad Jan
  • Jochen Herms
  • Poul H. SorensenEmail author
Review

Abstract

Messenger RNA (mRNA) translation is the terminal step in protein synthesis, providing a crucial regulatory checkpoint for this process. Translational control allows specific cell types to respond to rapid changes in the microenvironment or to serve specific functions. For example, neurons use mRNA transport to achieve local protein synthesis at significant distances from the nucleus, the site of RNA transcription. Altered expression or functions of the various components of the translational machinery have been linked to several pathologies in the central nervous system. In this review, we provide a brief overview of the basic principles of mRNA translation, and discuss alterations of this process relevant to CNS disease conditions, with a focus on brain tumors and chronic neurological conditions. Finally, synthesizing this knowledge, we discuss the opportunities to exploit the biology of altered mRNA translation for novel therapies in brain disorders, as well as how studying these alterations can shed new light on disease mechanisms.

Keywords

mRNA translation RNA-binding proteins Neurodegenerative diseases Brain tumors eEF2 kinase Translation control 

Notes

Funding

This work was partially supported by Canadian Cancer Society Research Institute (CCSRI) Impact Grant (Grant #703205; to PHS), and CIHR Foundation Grant FDN-143280 (to PHS). AD is supported by a Harry and Florence Dennison Fellowship in Medical Research, 4 Year Fellowship, and a Killam Doctoral Scholarship from the University of British Columbia, BC, Canada. Funding to AJ was in the form of an AIAS-COFUND fellowship from European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie agreement (Grant #754513) and the Lundbeckfonden, Denmark (Grant #R250-2017-1131).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular OncologyBritish Columbia Cancer Research CentreVancouverCanada
  2. 2.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  3. 3.Department of Biomedicine, Aarhus Institute of Advanced StudiesAarhus UniversityAarhus CDenmark
  4. 4.Department for Translational Brain ResearchGerman Center for Neurodegenerative Diseases (DZNE)MunichGermany
  5. 5.Center for Neuropathology and Prion ResearchLudwig-Maximilians-UniversityMunichGermany
  6. 6.Munich Cluster of Systems Neurology (SyNergy)Ludwig-Maximilians-University MunichMunichGermany

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