Sporadic inclusion-body myositis and hereditary inclusion-body myopathies: diseases of oxidative stress and aging?

Abstract

Sporadic inclusion-body myositis and hereditary inclusion-body myopathies are progressive and highly debilitating muscle diseases. The most characteristic morphologic feature of sporadic inclusion-body myositis and hereditary inclusion-body myopathies is vacuolar degeneration of muscle fibers, accompanied by intrafiber clusters (“tangles”) of paired-helical filaments and by accumulation of several proteins that are characteristic of a brain of patients with Alzheimer disease. In neither the hereditary inclusion-body myopathies nor sporadic inclusion-body myositis are the sequential steps of the pathogenic cascade understood. The several forms of hereditary inclusion-body myopathies have different genetic transmissions and probably different genetic defects. Because the sporadic inclusion-body myositis and hereditary inclusion-body myopathies have several characteristic pathologic features in common, we postulate that their different causes trigger the same upstream aberration leading to a similar downstream cascade of pathologic events, which are ultimately responsible for the characteristic muscle-fiber degeneration. We propose that important contributory factors leading to the inclusion-body myositis‐specific muscle fiber destruction are muscle aging and oxidative stress, putatively induced by the upstream overexpression of b-amyloid precursor protein within abnormal muscle fibers.