Effect of p75 neurotrophin receptor antagonist on disease progression in transgenic amyotrophic lateral sclerosis mice

Abstract

Neurotrophin level imbalances and altered p75 neurotrophin receptor (p75NTR) expression are implicated in spinal motor neuron degeneration in human and mouse models of amyotrophic lateral sclerosis (ALS). Recently, elevated reactive astrocyte-derived nerve growth factor (NGF) was linked to p75NTR-expressing motor neuron death in adult transgenic ALS mice. To test the role of NGF-dependent p75NTR-mediated signalling in ALS, we examined the effects of a cyclic decapeptide antagonist of p75NTR ligand binding by using neurotrophin-stimulated cell death assays and transgenic ALS mice. Murine motor neuron-like (NSC-34) cell cultures expressed full-length and truncated p75NTR, tyrosine receptor kin..