A study on the HSF2-mediated suppression mechanism of neurodegenerative diseases based on mouse models.

热休克转录因子(HSF2)是大脑皮质发育过程中重要的HSF，在中枢神经系统中高表达，但能否抑制细胞应激和变性蛋白介导的毒性引起的神经退行性疾病。在这一大辅助手段的支持下，首席研究人员揭示了HSF2可以抑制变性或未折叠的蛋白质引起的细胞内聚集。我们还分析了HSF2介导的细胞保护的新机制。虽然在四种HSFs中只有HSF1具有染色质开放和转录激活的能力，但在HSF1缺失的细胞中，其中一些新的HSF2靶基因可以单独被HSF2激活。这些结果表明，HSF2和HSF1一样具有染色质开放活性，诱导参与有毒蛋白降解的新的HSF2基因可以抑制神经退行性疾病。

The heat shock transcription factor (heat shock factor) HSF2 is an important HSF for cortical development and highly-expressed in CNS, however, whether it can suppress cellular stress and denatured protein-mediated toxicity causing neurodegenerative diseases or not. By the support of this grand-in-aid, the principal investigator revealed that HSF2 can suppress the intracellular aggregation caused by denatured or unfolded protein. We also analyzed the novel mechanism of HSF2-mediated cytoprotection. Although only HSF1 has chromatin opening and transcription activating ability among four HSFs, some of these novel HSF2 target genes were activated by HSF2 alone in the HSF1-deficient cells. These results suggest that HSF2 has the chromatin opening activity as well as HSF1, and that the induction of novel HSF2 regulated genes involved in toxic protein degradation can lead to the suppression of neurodegenerative diseases.