Muscle protein misfolding

Squire,J. (1981). The Structural Basis of Muscle Contraction. Plenum Press, New York. Stefani, M., and Dobson, C. M. (2003). Protein aggregation and aggregate toxicity New insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81, 678-699. 

Abnormal aggregations of misfolded protein molecules stainable with the fluorescence Congo red method of Askanas [90], or more simply but less inclusively with crystal violet, are called "amyloid." The amyloid in skeletal mnsde tissue can be (a) extracellular, usually in mnsde connective tissue regions or in blood-vessel walls, including blood vessels of peripheral nerves or (b) intracellular (within muscle fibers) of s-IBM (see Chapters 7 and 10). Musde extracellular amyloid is often composed of the variable portion of an immunoglobulin light chain, or mutant transthyretin, but sometimes other proteins are involved primarily or secondarily. (Extracellular amyloid can be clinically identified, noninvasively, by Mibi radioisotope scanning [91]). We have previously postulated that cyto-disturbance... 

Abnormal accumulation of ubiquitinated intracellular proteinadous indusions is characteristic of the s-IBM phenotype, thus s-EBM, similarly to Alzheimer and Parkinson disease, is considered a "conformational disorder," caused by protein un-folding/misfolding and associated with formation of proteinadous indusion bodies (reviewed in [1-4]). Similarly to Alzheimer and Parkinson brains, the sequence of the detrimental pathologic events comprising cellular degeneration in s-IBM musde fibers is not yet weU delineated. However, several aspects of the s-EBM intra-muscle-fiber pathogenic cascade are being uncovered and their causative mechanisms elucidated. 

BR stress most likely is induced in s-IBM muscle fibers by the accumulation of numerous misfolded proteins, as delineated above. In addition, oxidative and nitrosative stresses, and cholesterol accumulation, are known to occur in s-IBM muscle fibers [3, 55, 72], and in other systems they have been shown to lead to BR stress [191-193],... 

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