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Brain Res. 2018 Aug 15;1693(Pt A):75-91. doi: 10.1016/j.brainres.2018.02.018. Epub 2018 Feb 17.

mRNP assembly, axonal transport, and local translation in neurodegenerative diseases.

Author information

1
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 USA.
2
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 USA; Department of Cell Biology, Emory University, Atlanta, GA 30322 USA.
3
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 USA; Eye Center, The Second Hospital of Jilin University, Changchun, Jilin 130021, China.
4
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 USA. Electronic address: Rossoll.Wilfried@mayo.edu.

Abstract

The development, maturation, and maintenance of the mammalian nervous system rely on complex spatiotemporal patterns of gene expression. In neurons, this is achieved by the expression of differentially localized isoforms and specific sets of mRNA-binding proteins (mRBPs) that regulate RNA processing, mRNA trafficking, and local protein synthesis at remote sites within dendrites and axons. There is growing evidence that axons contain a specialized transcriptome and are endowed with the machinery that allows them to rapidly alter their local proteome via local translation and protein degradation. This enables axons to quickly respond to changes in their environment during development, and to facilitate axon regeneration and maintenance in adult organisms. Aside from providing autonomy to neuronal processes, local translation allows axons to send retrograde injury signals to the cell soma. In this review, we discuss evidence that disturbances in mRNP transport, granule assembly, axonal localization, and local translation contribute to pathology in various neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD).

KEYWORDS:

ALS; Axonal transport; Local translation; SMA; mRNA transport; mRNP assembly

PMID:
29462608
PMCID:
PMC5997521
[Available on 2019-08-15]
DOI:
10.1016/j.brainres.2018.02.018

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