在近期发生的精神分裂症中,ERVW-1通过降低GANAB来激活ATF6介导的未折叠蛋白反应
Xing Xue1, Xiulin Wu1, Lijuan Liu1,2
1State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Viruses
|June 28, 2023
概括
内源性逆转录病毒W成员1包裹 (ERVW-1) 通过抑制GANAB,上调ATF6和XBP1.1,在精神分裂症中提高内质网膜 (ER) 压力. 这种机制有助于精神分裂症的发展.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 精神分裂症影响全球人口的1%,其中包括内分泌网膜 (ER) 恒温失调.
- 经期应激和未折叠蛋白反应 (UPR) 越来越多地与精神分裂症有关.
- 已观察到内源性逆转录病毒组W成员1包裹 (ERVW-1) 的升高,这是精神分裂症的危险因素,但其与ER压力的联系尚不清楚.
研究的目的:
- 研究ER压力和精神分裂症中的ERVW-1之间的分子机制.
- 在精神分裂症患者的前额叶皮质中识别与UPR相关的差异表达基因 (DEG).
- 阐明ERVW-1在ER压力中的作用及其对精神分裂症病原体的贡献.
主要方法:
- 在人类前额叶皮层的基因差异表达分析.
- 基因表达的斯皮尔曼相关性分析.
- 与酶相关的免疫吸收试验 (ELISA) 检测血清蛋白水平.
- 在体外实验和共聚焦显微镜.
主要成果:
- 在精神分裂症患者中,UPR基因的异常表达,包括XBP1,ATF6,BCL-2和ERVW-1之间的正相关性.
- 血清ATF6和XBP1的增加,患者的GANAB降低,与ERVW-1水平相关.
- 在体外:ERVW-1增加了ATF6/XBP1和减少了GANAB,影响了ER形态和诱导ER压力.
结论:
- 通过抑制GANAB表达,ERVW-1诱导了ER压力.
- 这种抑制会提高ATF6和XBP1的调节,从而导致精神分裂症的发展.
- 针对ERVW-1/GANAB/ATF6/XBP1通路可能为精神分裂症提供治疗策略.
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