Dysfunction of RNA metabolism in TDP-43 proteinopathies: Elucidation of mechanism in stress granule formaion

应激颗粒是细胞在应激时出现的由RNA和RNA结合蛋白组成的细胞质中的致密聚集体。为了阐明应激颗粒形成在神经退行性疾病的疾病过程中的意义，我们检测了tau蛋白病、突触核蛋白病、TDP-43蛋白病和多聚谷氨酰胺疾病中应激颗粒标志物蛋白的免疫反应性。细胞质和核包涵体被证明是应激颗粒标记蛋白的免疫阳性，从而导致应激颗粒在神经退行性疾病的发展中对疾病机制起重要作用的假设。这些包涵体也与家族性肌萎缩侧索硬化症（fALS），TDP-43蛋白质病之一相关的一些蛋白免疫阳性。这些结果表明，应激颗粒标记蛋白和fALS相关蛋白可能是预防神经退行性疾病的治疗靶点。

Stress granules are dense aggregations in the cytosol composed of RNAs and RNA binding proteins that appear when the cell is under stress. To elucidate the significance of stress granule formation in the disease process of neurodegenerative diseases, we examined immunoreactivity for stress granule marker proteins in tauopathies, synucleinopathies, TDP-43 proteinopathies and polyglutamine diseases. Cytoplasmic and nuclear inclusions proved to be immunopositive for stress granule marker proteins, leading to the hypothesis that stress granules play important roles for disease mechanisms in the development of neurodegenerative diseases. These inclusions were also immunopositive for some proteins associated with familial amyotrophic lateral sclerosis (fALS), one of TDP-43 proteinopathies. These results suggested that stress granules marker proteins and fALS-associated proteins may be therapeutic targets to prevent neurodegenerative diseases.