Protein aggregate myopathies.
Protein aggregate myopathies.
复制标题
蛋白质聚集性肌病。
作者：
HH Goebel;MC Sharma
蛋白聚集性肌病（PAM）是一组以结构异常为特征的新兴肌肉疾病。蛋白质聚集性肌病的特征在于肌纤维内内在蛋白质的聚集，并分为四个主要组或病症：（1）结蛋白相关肌病（DRM），包括结蛋白病、a-B stac病、由a-B晶体蛋白和硒蛋白N1基因突变引起的硒蛋白病，（2）遗传性包涵体肌病，其中几种与不同的染色体基因座有关，但蛋白产物尚未鉴定，（3）以肌节ACTA 1基因突变为标志的放线菌病，和（4）以MYH-7基因突变为标志的肌球蛋白病。而PAM 1型和2型可能是基于受损的溶酶体外蛋白降解，导致大量不同蛋白的积累（在家族类型中，除了相应的突变蛋白质之外），PAM形式3和4可能代表合成代谢或发育缺陷，因为在肌动蛋白和肌球蛋白聚集体之外保留了肌节，并且在这些肌动蛋白或肌球蛋白聚集体中缺乏或不存在其他蛋白质，分别在PAM的假定分解代谢和合成代谢形式中，支配肌纤维内蛋白质聚集和随后的结构肌节的致病原理在很大程度上仍然未知。在其他先天性肌病中存在的内含物及其蛋白质组成，如还原体、圆柱螺旋、管状聚集体等，有待澄清。迄今为止所描述的PAM首先通过蛋白质的免疫组织化学和随后通过其基因的分子分析来鉴定。
Protein aggregate myopathies (PAM) are an emerging group of muscle diseases characterized by structural abnormalities. Protein aggregate myopathies are marked by the aggregation of intrinsic proteins within muscle fibers and fall into four major groups or conditions: (1) desmin-related myopathies (DRM) that include desminopathies, a-B crystallinopathies, selenoproteinopathies caused by mutations in the, a-B crystallin and selenoprotein N1 genes, (2) hereditary inclusion body myopathies, several of which have been linked to different chromosomal gene loci, but with as yet unidentified protein product, (3) actinopathies marked by mutations in the sarcomeric ACTA1 gene, and (4) myosinopathy marked by a mutation in the MYH-7 gene. While PAM forms 1 and 2 are probably based on impaired extralysosomal protein degradation, resulting in the accumulation of numerous and diverse proteins (in familial types in addition to respective mutant proteins), PAM forms 3 and 4 may represent anabolic or developmental defects because of preservation of sarcomeres outside of the actin and myosin aggregates and dearth or absence of other proteins in these actin or myosin aggregates, respectively. The pathogenetic principles governing protein aggregation within muscle fibers and subsequent structural sarcomeres are still largely unknown in both the putative catabolic and anabolic forms of PAM. Presence of inclusions and their protein composition in other congenital myopathies such as reducing bodies, cylindrical spirals, tubular aggregates and others await clarification. The hitherto described PAMs were first identified by immunohistochemistry of proteins and subsequently by molecular analysis of their genes.