Lysosomal myopathies: An excessive build-up in autophagosomes is too much to handle

Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Neuromuscular Disorders (Impact Factor: 2.64). 08/2008; 18(7):521-9. DOI: 10.1016/j.nmd.2008.04.010
Source: PubMed


Lysosomes are membrane-bound acidic organelles that contain hydrolases used for intracellular digestion of various macromolecules in a process generally referred to as autophagy. In normal skeletal and cardiac muscles, lysosomes usually appear morphologically unremarkable and thus are not readily visible on light microscopy. In distinct neuromuscular disorders, however, lysosomes have been shown to be structurally abnormal and functionally impaired, leading to the accumulation of autophagic vacuoles in myofibers. More specifically, there are myopathies in which buildup of these autophagic vacuoles seem to predominate the pathological picture. In such conditions, autophagy is considered not merely a secondary event, but a phenomenon that actually contributes to disease pathomechanism and/or progression. At present, there are two disorders in the muscle which are associated with primary defect in lysosomal proteins, namely Danon disease and Pompe disease. Other myopathies which have prominent autophagy in the skeletal muscle include X-linked myopathy with excessive autophagy (XMEA). In this review, these disorders are briefly characterized, and the role of autophagy in the context of the pathomechanism of these disorders is highlighted.

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    • "Autophagy is intricately implicated in both health and disease. Autophagy defects play a role in the pathogenesis of diverse diseases, including myopathy, neuronal degeneration, microbial infection, inflammatory bowel disease, aging, and cancer (Cadwell et al., 2008; Malicdan et al., 2008; Saitoh et al., 2008; Winslow and Rubinsztein, 2008; Yen and Klionsky, 2008; Orvedahl and Levine, 2009). Recent studies have elucidated the functional role of autophagy in different cellular processes and the potential of autophagy modulation as a novel therapeutic strategy for different pathologic conditions, including cancer (Carew et al., 2007; Mathew et al., 2007; Chen and Karantza-Wadsworth, 2009). "
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