ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons

Zachary Osking, Jacob I. Ayers, Ryan Hildebrandt, Kristen Skruber, Hilda Brown, Daniel Ryu, Amanda R. Eukovich, Todd E. Golde, David R. Borchelt, Tracy Ann Read, Eric A. Vitriol

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by motor neuron cell death. However, not all motor neurons are equally susceptible. Most of what we know about the surviving motor neurons comes from gene expression profiling; less is known about their functional traits. We found that resistant motor neurons cultured from SOD1 ALS mouse models have enhanced axonal outgrowth and dendritic branching. They also have an increase in the number and size of actin-based structures like growth cones and filopodia. These phenotypes occur in cells cultured from presymptomatic mice and mutant SOD1 models that do not develop ALS but not in embryonic motor neurons. Enhanced outgrowth and upregulation of filopodia can be induced in wild-type adult cells by expressing mutant SOD1. These results demonstrate that mutant SOD1 can enhance the regenerative capability of ALS-resistant motor neurons. Capitalizing on this mechanism could lead to new therapeutic strategies. Biological Sciences; Genetics; Neuroscience; Cell Biology

Original languageEnglish (US)
Pages (from-to)294-304
Number of pages11
JournaliScience
Volume11
DOIs
StatePublished - Jan 25 2019
Externally publishedYes

Keywords

  • Biological Sciences
  • Cell Biology
  • Genetics
  • Neuroscience

ASJC Scopus subject areas

  • General

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