Institut de Neurociències (INc) and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), Bellaterra, 08193 Barcelona, Spain.
Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain.
Cells. 2020 Jun 28;9(7):1575. doi: 10.3390/cells9071575.
Muscle wasting is an unmet medical need which leads to a reduction of myofiber diameter and a negative impact on the functional performance of daily activities. We previously found that a new neuroprotective drug called NeuroHeal reduced muscle atrophy produced by transient denervation. Aiming to decipher whether NeuroHeal has a direct role in muscle biology, we used herein different models of muscle atrophy: one caused by chronic denervation, another caused by hindlimb immobilization, and lastly, an in vitro model of myotube atrophy with Tumor Necrosis Factor-α (TNFα). In all these models, we observed that NeuroHeal reduced muscle atrophy and that SIRT1 activation seems to be required for that. The treatment downregulated some critical markers of protein degradation: Muscle Ring Finger 1 (MuRF1), K48 poly-Ub chains, and p62/SQSTM1. Moreover, it seems to restore the autophagy flux associated with denervation. Hence, we envisage a prospective use of NeuroHeal at clinics for different myopathies.
肌肉萎缩是一种未满足的医学需求，它会导致肌纤维直径减小，并对日常活动的功能表现产生负面影响。我们之前发现，一种名为 NeuroHeal 的新型神经保护药物可减少短暂失神经引起的肌肉萎缩。为了解 NeuroHeal 是否对肌肉生物学有直接作用，我们在此使用了不同的肌肉萎缩模型：一种由慢性失神经引起，另一种由后肢固定引起，最后是体外肌管萎缩模型，使用肿瘤坏死因子-α（TNFα）。在所有这些模型中，我们观察到 NeuroHeal 可减少肌肉萎缩，而 SIRT1 的激活似乎是必需的。该治疗方法下调了一些关键的蛋白降解标志物：肌肉环指蛋白 1（MuRF1）、K48 多聚泛素链和 p62/SQSTM1。此外，它似乎恢复了与失神经相关的自噬通量。因此，我们设想在临床上将 NeuroHeal 用于治疗不同的肌肉疾病。
