Cutler Alicia A, Ewachiw Theodore Eugene, Corbet Giulia A, Parker Roy, Olwin Brad B
Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
J Exp Neurosci. 2019 Apr 12;13:1179069519842157. doi: 10.1177/1179069519842157. eCollection 2019.
A hallmark of many neuromuscular diseases including Alzheimer disease, inclusion body myositis, amyotrophic lateral sclerosis, frontotemporal lobar dementia, and ocular pharyngeal muscular dystrophy is large cytoplasmic aggregates containing the RNA-binding protein, TDP-43. Despite acceptance that cytoplasmic TDP-43 aggregation is pathological, cytoplasmic TDP-43 assemblies form in healthy regenerating muscle. These recently discovered ribonucleoprotein assemblies, termed myo-granules, form in healthy muscle following injury and are readily cleared as the myofibers mature. The formation and dissolution of myo-granules during normal muscle regeneration suggests that these amyloid-like oligomers may be functional and that perturbations in myo-granule kinetics or composition may promote pathological aggregation.
许多神经肌肉疾病的一个标志，包括阿尔茨海默病、包涵体肌炎、肌萎缩侧索硬化症、额颞叶痴呆和眼咽型肌营养不良，是含有RNA结合蛋白TDP - 43的大细胞质聚集体。尽管人们普遍认为细胞质TDP - 43聚集是病理性的，但在健康的再生肌肉中会形成细胞质TDP - 43聚集体。这些最近发现的核糖核蛋白聚集体，称为肌颗粒，在受伤后的健康肌肉中形成，并在肌纤维成熟时很容易被清除。正常肌肉再生过程中肌颗粒的形成和溶解表明，这些淀粉样寡聚体可能具有功能，并且肌颗粒动力学或组成的扰动可能会促进病理性聚集。
