AMPK regulates the maintenance and remodelling of the neuromuscular junction.

Objective: The molecular mechanisms underlying the maintenance and adaptability of the neuromuscular junction (NMJ) remain poorly understood. This study aimed to investigate the role of AMP-activated protein kinase (AMPK) as a key regulator of NMJ stability and plasticity.

Method: A comprehensive, multifaceted approach was employed, integrating genetic, physiological, and pharmacological methodologies to elucidate the role of skeletal muscle AMPK in modulating the neuromuscular synapse.

Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females.

Androgen receptor (AR) content has been implicated in the differential response between high and low responders following resistance exercise training (RET). However, the influence of AR expression on acute skeletal muscle damage and whether it may influence the adaptive response to RET in females is poorly understood. Thus, the purpose of this exploratory examination was to 1) investigate changes in AR content during skeletal muscle repair and 2) characterize AR-mediated sex-based differences following RET.

CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.

CARM1 (coactivator associated arginine methyltransferase 1) has recently emerged as a powerful regulator of skeletal muscle biology. However, the molecular mechanisms by which the methyltransferase remodels muscle remain to be fully understood. In this study, skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253).

Sex-Specific Effect of CARM1 in Skeletal Muscle Adaptations to Exercise.

Purpose: The purpose of this study was to determine how the intersection of coactivator-associated arginine methyltransferase 1 (CARM1) and biological sex affects skeletal muscle adaptations to chronic physical activity.

Methods: Twelve-week-old female (F) and male (M) wild-type (WT) and CARM1 skeletal muscle-specific knockout (mKO) mice were randomly assigned to sedentary (SED) or voluntary wheel running (VWR) experimental groups. For 8 wk, the animals in the VWR cohort had volitional access to running wheels.

Impact of short-term, pharmacological CARM1 inhibition on skeletal muscle mass, function, and atrophy in mice.

Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins critical for health and disease. The purpose of this study was to characterize the effects of short-term, pharmacological CARM1 inhibition on skeletal muscle size, function, and atrophy. Adult mice ( = 10 or 11/sex) were treated with either a CARM1 inhibitor (150 mg/kg EZM2302; EZM) or vehicle (Veh) via oral gavage for 11-13 days and muscle mass, function, and exercise capacity were assessed.

AMPK is mitochondrial medicine for neuromuscular disorders.

Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and spinal muscular atrophy (SMA) are the most prevalent neuromuscular disorders (NMDs) in children and adults. Central to a healthy neuromuscular system are the processes that govern mitochondrial turnover and dynamics, which are regulated by AMP-activated protein kinase (AMPK). Here, we survey mitochondrial stresses that are common between, as well as unique to, DMD, DM1, and SMA, and which may serve as potential therapeutic targets to mitigate neuromuscular disease.

Acute, next-generation AMPK activation initiates a disease-resistant gene expression program in dystrophic skeletal muscle.

Duchenne muscular dystrophy (DMD) is a life-limiting neuromuscular disorder characterized by muscle weakness and wasting. Previous proof-of-concept studies demonstrate that the dystrophic phenotype can be mitigated with the pharmacological stimulation of AMP-activated protein kinase (AMPK). However, first-generation AMPK activators have failed to translate from bench to bedside due to either their lack of potency or toxic, off-target effects.

A single dose of exercise stimulates skeletal muscle mitochondrial plasticity in myotonic dystrophy type 1.

Aim: Myotonic dystrophy type 1 (DM1) is the second most common muscular dystrophy after Duchenne and is the most prevalent muscular dystrophy in adults. DM1 patients that participate in aerobic exercise training experience several physiological benefits concomitant with improved muscle mitochondrial function without alterations in typical DM1-specific disease mechanisms, which suggests that correcting organelle health is key to ameliorate the DM1 pathology. However, our understanding of the molecular mechanisms of mitochondrial turnover and dynamics in DM1 skeletal muscle is lacking.

The CARM1 transcriptome and arginine methylproteome mediate skeletal muscle integrative biology.

Objective: Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins to regulate critical processes in health and disease. A mechanistic understanding of the role(s) of CARM1 in skeletal muscle biology is only gradually emerging. The purpose of this study was to elucidate the function of CARM1 in regulating the maintenance and plasticity of skeletal muscle.

Aerobic exercise elicits clinical adaptations in myotonic dystrophy type 1 patients independently of pathophysiological changes.

BackgroundMyotonic dystrophy type 1 (DM1) is a complex life-limiting neuromuscular disorder characterized by severe skeletal muscle atrophy, weakness, and cardiorespiratory defects. Exercised DM1 mice exhibit numerous physiological benefits that are underpinned by reduced CUG foci and improved alternative splicing. However, the efficacy of physical activity in patients is unknown.