Death receptor 6 (DR6) antagonist antibody is neuroprotective in the mouse SOD1G93A model of amyotrophic lateral sclerosis.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons, axon degeneration, and denervation of neuromuscular junctions (NMJ). Here we show that death receptor 6 (DR6) levels are elevated in spinal cords from post-mortem samples of human ALS and from SOD1(G93A) transgenic mice, and DR6 promotes motor neuron death through activation of the caspase 3 signaling pathway. Blocking DR6 with antagonist antibody 5D10 promotes motor neuron survival in vitro via activation of Akt phosphorylation and inhibition of the caspase 3 signaling pathway, after growth factor withdrawal, sodium arsenite treatment or co-culture with SOD1(G93A) astrocytes. Treatment of SOD1(G93A) mice at an asymptomatic stage starting on the age of 42 days with 5D10 protects

SUBMITTER: Huang G 

PROVIDER: S-EPMC3824687 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature