ALS Along the Axons - Expression of Coding and Noncoding RNA Differs in Axons of ALS models. Academic Article uri icon

Overview

abstract

  • Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA). Further, the introduction of SOD1G93A and TDP43A315T, established ALS-related mutations, changed the subcellular expression and localization of RNAs within the neurons, showing a spatial specificity to either the soma or the axon. Altogether, we provide here the first combined inclusive profile of mRNA and miRNA expression in two ALS models at the subcellular level. These data provide an important resource for studies on the roles of local protein synthesis and axon degeneration in ALS and can serve as a possible target pool for ALS treatment.

publication date

  • March 16, 2017

Research

keywords

  • Amyotrophic Lateral Sclerosis
  • Axons
  • DNA-Binding Proteins
  • Superoxide Dismutase-1

Identity

PubMed Central ID

  • PMC5353576

Scopus Document Identifier

  • 85015378121

Digital Object Identifier (DOI)

  • 10.1016/j.ijdevneu.2016.03.004

PubMed ID

  • 28300211

Additional Document Info

volume

  • 7