English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (ALS) in humans. ALS is a neurodegenerative disease characterized by progressive motor neuron loss leading to paralysis and inevitable death in affected individuals. Using a gene replacement strategy to introduce disease mutations into the orthologous Drosophila sod1 ( dsod1 ) gene, here, we characterize changes at the neuromuscular junction using longer-lived dsod1 mutant adults. Homozygous dsod1 H71Y/H71Y  or dsod1 null/null  flies display progressive walking defects with paralysis of the third metathoracic leg. In dissected legs, we assessed age-dependent changes in a single identified motor neuron (MN-I2) innervating the tibia levitator muscle. At adult eclosion, MN-I2 of dsod1 H71Y/H71Y  or sod1 null/null  flies is patterned similar to wild-type flies indicating no readily apparent developmental defects. Over the course of 10 days post-eclosion, MN-I2 shows an overall reduction in arborization with bouton swelling and loss of the post-synaptic marker discs-large ( dlg ) in mutant dsod1 adults. In addition, increases in polyubiquitinated proteins correlate with the timing and extent of MN-I2 changes. Because similar phenotypes are observed between flies homozygous for either dsod1 H71Y  or dsod1 null  alleles, we conclude these NMJ changes are mainly associated with sod loss-of-function. Together these studies characterize age-related morphological and molecular changes associated with axonal retraction in a Drosophila model of ALS that recapitulate an important aspect of the human disease.This article has an associated First Person interview with the first author of the paper.

Age-dependent degeneration of an identified adult leg motor neuron in a Drosophila SOD1 model of ALS