SGTA associates with intracellular aggregates in neurodegenerative diseases.
SGTA associates with intracellular aggregates in neurodegenerative diseases.
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DOI：
10.1186/s13041-021-00770-1
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发表时间：
2021-03-23
期刊：
影响因子：
3.6
通讯作者：
Tanaka F
中科院分区：
文献类型：
--
作者：
Kubota S;Doi H;Koyano S;Tanaka K;Komiya H;Katsumoto A;Ikeda S;Hashiguchi S;Nakamura H;Fukai R;Takahashi K;Kunii M;Tada M;Takeuchi H;Tanaka F
细胞内聚集是神经退行性疾病的常见病理标志，例如多谷氨酰胺 (polyQ) 疾病、肌萎缩侧索硬化症 (ALS)、帕金森病 (PD) 和多系统萎缩症 (MSA)。聚集体主要由异常的疾病特异性蛋白形成，并伴有其他聚集体相互作用蛋白的积累。尽管聚集体相互作用蛋白被认为可以调节聚集体的形成并参与疾病进展的分子机制，但聚集体相互作用蛋白的成分仍然未知。在这项研究中，我们发现富含谷氨酰胺的小四肽重复序列蛋白α（SGTA）是神经退行性疾病中的一种聚集相互作用蛋白。免疫组织化学显示，SGTA 与亨廷顿病 (HD) 细胞模型和 HD 模型小鼠神经元中的细胞内聚集体相互作用。我们还发现，SGTA 与患有 PolyQ 疾病（包括脊髓小脑共济失调（SCA）1、SCA2、SCA3 和齿状红核-苍白球路易体萎缩）患者死后大脑中的细胞内聚集物共定位。此外，SGTA 与 MSA 患者大脑中的神经胶质细胞质内含物共定位，而在 PD 和 ALS 患者的神经元中没有观察到 SGTA 的积累。体外研究表明，SGTA 通过其 C 端结构域与 PolyQ 聚集体结合，并且 SGTA 过表达会减少细胞内聚集体。这些结果表明，SGTA 可能在聚集体的形成中发挥作用，并可能作为 PolyQ 疾病和 MSA 分子病理机制的潜在修饰剂。在线版本包含可在 10.1186/s13041-021-00770-1 获取的补充材料。
Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral–pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA. The online version contains supplementary material available at 10.1186/s13041-021-00770-1.
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影响因子：
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作者：
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影响因子：
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作者：
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