Journal
CURRENT OPINION IN PHARMACOLOGY
Volume 60, Issue -, Pages 193-199Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.coph.2021.07.023
Keywords
MAFbx; Atrogin-1; MuRF1; FOXO; Ubiquitin; mTOR; Hypertrophy; Alrophy; Anabolic; Spinal cord injury; Disuse; Unloading; Denervation; Paralysis; Paralyzed; Muscle; Musculoskeletal; Testosterone; Testosterone replacement therapy; Androgen; Insulin-like growth factor 1; Igf1; Myostatin; Activin IIb receptor; Transforming growth factor beta; TGF beta; Beta 2 agonist; Clenbuterol; Formoterol; Ursolic acid; SS-31; Elamipretide; Antioxidant; Epicatechin; Acteoside; Verbascoside; Activity-based physical therapy; Functional electrical stimulation; Neuro muscular electrical stimulation; Bodyweight-supported treadmill training
Categories
Funding
- Department of Veterans Affairs Office of Research and Development, Rehabilitation Research and Development Service Merit Award [1I01RX002447-01]
- PECASE [B9280-O]
- CDA-2 [IK2RX002781]
Ask authors/readers for more resources
Muscle atrophy is a common result of severe spinal cord injury, driven by signaling cascades such as ubiquitinproteasome signaling. Strategies combining physical rehabilitation regimens with drug targeting molecular pathways hold the greatest potential to improve muscle recovery after SCI.
Skeletal muscle atrophy is a hallmark of severe spinal cord injury (SCI) that is precipitated by the neural insult and paralysis. Additionally, other factors may influence muscle loss, including systemic inflammation, low testosterone, low insulin-like growth factor (IGF)-1, and high-dose glucocorticoid treatment. The signaling cascades that drive SCI-induced muscle loss are common among most forms of disuse atrophy and include ubiquitinproteasome signaling and others. However, differing magnitudes and patterns of atrophic signals exist after SCI versus other disuse conditions and are accompanied by endogenous inhibition of IGF1/PI3K/Akt signaling, which combine to produce exceedingly rapid atrophy. Several well-established anabolic agents, including androgens and myostatin inhibitors, display diminished ability to prevent SCI-induced atrophy, while ursolic acid and b2-agonists more effectively attenuate muscle loss. Strategies combining physical rehabilitation regimens to reload the paralyzed limbs with drugs targeting the underlying molecular pathways hold the greatest potential to improve muscle recovery after severe SCI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available