Timing of proteasome inhibition as a pharmacologic strategy for prevention of muscle contractures in neonatal brachial plexus injury.

ABSTRACT: Neonatal brachial plexus injury (NBPI) causes disabling and incurable contractures, or limb stiffness, which result from proteasome-mediated protein degradation impairing the longitudinal growth of neonatally denervated muscles. We recently showed in a mouse model that the 20S proteasome inhibitor, bortezomib, prevents contractures after NBPI. Given that contractures uniquely follow neonatal denervation, the current study tests the hypothesis that proteasome inhibition during a finite window of neonatal development can prevent long-term contracture development. Following neonatal forelimb denervation in P5 mice, we first outlined the minimum period for proteasome inhibition to prevent contractures 4 weeks post-NBPI by treating mice with saline or bortezomib for varying durations between P8

SUBMITTER: Goh Q 

PROVIDER: S-EPMC7821701 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature