Spinal motor neuron loss occurs through a p53-and-p21-independent mechanism in the Smn^2B/- mouse model of spinal muscular atrophy.

ABSTRACT: Spinal muscular atrophy (SMA) is a pediatric neuromuscular disease caused by genetic deficiency of the survival motor neuron (SMN) protein. Pathological hallmarks of SMA are spinal motor neuron loss and skeletal muscle atrophy. The molecular mechanisms that elicit and drive preferential motor neuron degeneration and death in SMA remain unclear. Transcriptomic studies consistently report p53 pathway activation in motor neurons and spinal cord tissue of SMA mice. Recent work has identified p53 as an inducer of spinal motor neuron loss in severe Δ7 SMA mice. Additionally, the cyclin-dependent kinase inhibitor P21 (Cdkn1a), an inducer of cell cycle arrest and mediator of skeletal muscle atrophy, is consistently increased in motor neurons, spinal cords, and other tissues of various SMA models.

SUBMITTER: Reedich EJ 

PROVIDER: S-EPMC7870563 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature