PT  - JOURNAL ARTICLE
AU  - Zachary Osking
AU  - Jacob I. Ayers
AU  - Ryan Hildebrandt
AU  - Kristen Skruber
AU  - Hilda Brown
AU  - Daniel Ryu
AU  - Amanda R. Eukovich
AU  - Todd E. Golde
AU  - David R. Borchelt
AU  - Tracy-Ann Read
AU  - Eric A. Vitriol
TI  - ALS-linked SOD1 Mutants Enhance Outgrowth, Branching, and the Formation of Actin-Based Structures in Adult Motor Neurons
AID  - 10.1101/303271
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 303271
4099  - http://biorxiv.org/content/early/2018/10/15/303271.short
4100  - http://biorxiv.org/content/early/2018/10/15/303271.full
AB  - 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.