Protein aggregate myopathies: the many faces of an expanding disease group

Excerpt

The physiological functions of proteins are highly dependent on their correct three-dimensional conformation. Disturbances in the proper folding of newly synthesized or pre-existing proteins as well as in pathways responsible for refolding (molecular chaperones) or degradation of misfolded proteins (ubiquitin–proteasome and autophagy systems) may lead to intra- and/or extracellular protein aggregation. These precipitates of misfolded proteins form either ordered (e.g., amyloid fibrils) or disordered (e.g., inclusion bodies) protein aggregates that dissociate only in the presence of high concentrations of detergents or denaturing buffers. Such protein aggregates are the characteristic pathomorphological feature in a wide variety of hereditary and acquired human diseases affecting the central nervous system (e.g., Alzheimer’s, Parkinson’s disease), the peripheral nervous system (e.g., giant axonal neuropathy, amyloidosis), the eye (e.g., cataracts), the skin (e.g., epidermolytic keratin diseases), the liver (e.g., α1-antitrypsin deficiency, alcoholic steatohepatitis), as well as the heart and skeletal muscle (e.g., desmin cardiomyopathy and myopathy). …