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Acta Neuropathol. 2019 Feb 9. doi: 10.1007/s00401-019-01971-8. [Epub ahead of print]

Translational control in brain pathologies: biological significance and therapeutic opportunities.

Author information

1
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada. adelaidelli@bccrc.ca.
2
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. adelaidelli@bccrc.ca.
3
Department of Biomedicine, Aarhus Institute of Advanced Studies, Aarhus University, Høegh-Guldbergs Gade 6B, 8000, Aarhus C, Denmark.
4
Department for Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
5
Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
6
Munich Cluster of Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich, Schillerstraße 44, 80336, Munich, Germany.
7
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada. psor@mail.ubc.ca.
8
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. psor@mail.ubc.ca.

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:

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

PMID:
30739199
DOI:
10.1007/s00401-019-01971-8

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