Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1^G93A ALS mouse model.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is an untreatable, progressive, neurodegenerative disease specifically affecting motor neurons. Recently, the tyrosine kinase receptor EphA4 was directly implicated in ALS disease progression. We report that a long-lived mutated form of the EphA4 antagonist EphA4-Fc (mutEphA4-Fc), which blocks EphA4 binding to its ligands and inhibits its function, significantly improved functional performance in SOD1^G93A ALS model mice, as assessed by rotarod and hind-limb grip strength tests. Further, heterozygous motor neuron-specific EphA4 gene deletion in SOD1^G93A mice promoted significant improvement in functional performance during the disease course and a delay in disease onset relative to control mice. Importantly, mice in the heterozygous

SUBMITTER: Zhao J 

PROVIDER: S-EPMC6065374 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature