粒体自噬
奥氮平
生物
线粒体
药理学
精神分裂症(面向对象编程)
神经科学
细胞生物学
医学
精神科
自噬
遗传学
细胞凋亡
作者
Xi Chen,Zhizhen Wang,Peng Zheng,Anjila Dongol,Yuanyi Xie,Xing Ge,Mingxuan Zheng,Xitong Dang,Zehra Boz Seyhan,Nages Nagaratnam,Yinghua Yu,Xu‐Feng Huang
出处
期刊:Aging Cell
[Wiley]
日期:2023-10-13
卷期号:22 (11)
被引量:2
摘要
Abstract The lifespan of schizophrenia patients is significantly shorter than the general population. Olanzapine is one of the most commonly used antipsychotic drugs (APDs) for treating patients with psychosis, including schizophrenia and bipolar disorder. Despite their effectiveness in treating positive and negative symptoms, prolonged exposure to APDs may lead to accelerated aging and cognitive decline, among other side effects. Here we report that dysfunctional mitophagy is a fundamental mechanism underlying accelerated aging induced by olanzapine, using in vitro and in vivo ( Caenorhabditis elegans ) models. We showed that the aberrant mitophagy caused by olanzapine was via blocking mitophagosome–lysosome fusion. Furthermore, olanzapine can induce mitochondrial damage and hyperfragmentation of the mitochondrial network. The mitophagosome–lysosome fusion in olanzapine‐induced aging models can be restored by a mitophagy inducer, urolithin A, which alleviates defective mitophagy, mitochondrial damage, and fragmentation of the mitochondrial network. Moreover, the mitophagy inducer ameliorated behavioral changes induced by olanzapine, including shortened lifespan, and impaired health span, learning, and memory. These data indicate that olanzapine impairs mitophagy, leading to the shortened lifespan, impaired health span, and cognitive deficits. Furthermore, this study suggests the potential application of mitophagy inducers as therapeutic strategies to reverse APD‐induced adverse effects associated with accelerated aging.
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