Wojcik S, Engel W K, Askanas V
USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA 90017-1912, USA.
Acta Myol. 2006 Dec;25(3):116-8.
Nogo (RTN4) belongs to the reticulon (RTN) family of integral membrane proteins. RTN4A (Nogo-A), RTN4B (Nogo-B) and RTN4C (Nogo-C) are isoforms of RTN4. In the gastrocnemius muscle of transgenic mice bearing an SOD1 mutation ("ALS model"), increased Nogo-A mRNA and protein was reported, and similar changes were reported in muscle biopsies of patients with amyotrophic lateral sclerosis (ALS) but not with peripheral neuropathy or primary muscle diseases, leading to the proposal that Nogo-A in skeletal muscle is a new specific molecular marker of ALS. Here we report, based on studies of muscle biopsies from patients with ALS, peripheral neuropathies, polymyositis, dermatomyositis and morphologically nonspecific myopathies that, in addition of strong Nogo-A immunoreactivity within apparently-denervated small angular fibers in ALS and peripheral neuropathies, Nogo-A was strongly immunoreactive within desmin-positive regenerating muscle fibers in various myopathies, and its expression on immunoblots was increased in all those neuromuscular diseases. In conclusion, we have found that the presence of Nogo-A in diseased human muscle biopsies is not limited to ALS.
Nogo(RTN4)属于整合膜蛋白的网织蛋白(RTN)家族。RTN4A(Nogo - A)、RTN4B(Nogo - B)和RTN4C(Nogo - C)是RTN4的同工型。在携带SOD1突变的转基因小鼠(“肌萎缩侧索硬化症模型”)的腓肠肌中,有报道称Nogo - A的mRNA和蛋白增加,在肌萎缩侧索硬化症(ALS)患者的肌肉活检中也报道了类似变化,但周围神经病变或原发性肌肉疾病患者中未出现类似变化,这使得人们提出骨骼肌中的Nogo - A是ALS的一种新的特异性分子标志物。在此,我们基于对ALS、周围神经病变、多发性肌炎、皮肌炎和形态学上非特异性肌病患者的肌肉活检研究报告,除了在ALS和周围神经病变中明显失神经支配的小角状纤维内有强烈的Nogo - A免疫反应性外,在各种肌病中结蛋白阳性的再生肌纤维内Nogo - A也有强烈免疫反应性,并且在所有这些神经肌肉疾病中其免疫印迹表达均增加。总之,我们发现患病人类肌肉活检中Nogo - A的存在并不局限于ALS。