Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax

多聚谷氨酰胺扩增干扰内质网形成,导致 caspase-7 通过 Bax 激活

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作者:Masashi Ueda, Shimo Li, Masanori Itoh, Yoshika Hayakawa-Yano, Miao-xing Wang, Miki Hayakawa, Ryoko Hasebe-Matsubara, Kazunori Ohta, Eri Ohta, Akihito Mizuno, Yoko Hida, Munekazu Matsumoto, Huayue Chen, Toshiyuki Nakagawa

Abstract

The endoplasmic reticulum (ER) plays a pivotal role in cellular functions such as the ER stress response. However, the effect of the ER membrane on caspase activation remains unclear. This study reveals that polyglutamine oligomers augmented at ER induce insertion of Bax into the ER membrane, thereby activating caspase-7. In line with the role of ER in cell death induced by polyglutamine expansion, the ER membrane was found to be disrupted and dilated in the brain of a murine model of Huntington's disease. We can conclude that polyglutamine expansion may drive caspase-7 activation by disrupting the ER membrane.

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