Dataset Information


Beta-agonist stimulation ameliorates the phenotype of spinal and bulbar muscular atrophy mice and patient-derived myotubes.

ABSTRACT: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the loss of lower motor neurons. SBMA is caused by expansions of a polyglutamine tract in the gene coding for androgen receptor (AR). Expression of polyglutamine-expanded AR causes damage to motor neurons and skeletal muscle cells. Here we investigated the effect of ?-agonist stimulation in SBMA myotube cells derived from mice and patients, and in knock-in mice. We show that treatment of myotubes expressing polyglutamine-expanded AR with the ?-agonist clenbuterol increases their size. Clenbuterol activated the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway and decreased the accumulation of polyglutamine-expanded AR. Treatment of SBMA knock-in mice with clenbuterol, which was started at disease onset, ameliorated motor function and extended survival. Clenbuterol improved muscle pathology, attenuated the glycolytic-to-oxidative metabolic alterations occurring in SBMA muscles and induced hypertrophy of both glycolytic and oxidative fibers. These results indicate that ?-agonist stimulation is a novel therapeutic strategy for SBMA.


PROVIDER: S-EPMC5259768 | BioStudies | 2017-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC2678926 | BioStudies
1000-01-01 | S-EPMC5409076 | BioStudies
| S-EPMC3881232 | BioStudies
2015-01-01 | S-EPMC4577982 | BioStudies
1000-01-01 | S-EPMC2644643 | BioStudies
2013-01-01 | S-EPMC3654311 | BioStudies
1000-01-01 | S-EPMC4305189 | BioStudies
1000-01-01 | S-EPMC6333819 | BioStudies
2020-01-01 | S-EPMC7072234 | BioStudies
2016-01-01 | S-EPMC4931718 | BioStudies