[Muscle pathologic diagnosis--mechanism in muscle fiber degeneration]

In various neuromuscular diseases, the most significant muscle degeneration is muscle fiber necrosis as seen in Duchenne muscular dystrophy (DMD). A certain membrane instability is probably responsible for muscle fiber necrosis, because defects in membrane proteins have been proposed to associate with progressive muscular dystrophies including dystrophin in DMD, a 50 KD subunit of dystrophin associated glycoprotein (DAG) in severe childhood autosomal recessive muscular dystrophy (SCARMD), and subunit M of laminin (merosin) in congenital muscular dystrophy and dy mouse. The vulnerable muscle surface membrane may permit extracellular calcium influx into the sarcoplasm resulting in focal myofibrillar hypercontraction (opaque fiber) and activation of proteases such as calpain and cathepsins. The muscle fiber then undergoes necrosis and allows macrophage invasion, followed by muscle fiber regeneration. Focal myofibrillar degeneration involving rimmed vacuole (RV) formation is an another striking muscle fiber degeneration seen in various neuromuscular diseases including inclusion body myositis (IBM) and distal myopathy with rimmed vacuole formation (DMRV). Abnormal accumulation of ubiquitin, beta-amyloid protein precursor and tau protein has been described in IBM by Askanas et al. The similar findings are also recognizable in DMRV and in an experimentally induced myopathy after long-term chloroquin administration to rat. Therefore, if we clarify the pathomechanism of degenerative process involved in the rimmed vacuole formation, the results may provide some insights into the understanding the process involved in amyloid plaque formation in Alzheimer's disease.