LYECs: lysosome-enhancing compounds as potential therapeutic approaches for Alzheimer disease.
LYECs: lysosome-enhancing compounds as potential therapeutic approaches for Alzheimer disease.
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DOI：
10.1080/15548627.2022.2131247
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发表时间：
2023-06
期刊：
影响因子：
13.3
通讯作者：
Li, Yang
中科院分区：
文献类型：
--
作者：
Yin, Limin;Zhou, Yu;Liu, Hong;Li, Yang
超过5500万人患有阿尔茨海默病(AD)，但仍然没有有效的治疗方法。因此，蛋白质质量控制的新的治疗方法和调控机制需要进一步的评价和剖析。溶酶体是维持细胞内环境平衡和蛋白质质量控制的主要降解细胞器之一。在我们最近的研究中，我们发现了一组溶酶体增强化合物(LYECs)，它们通过抑制多巴胺转运体(DAT)而显著促进转录因子EB(TFEB)的激活和溶酶体的生物生成。注射LH2-051，本研究中确定的LYECs成员，显著改善APP-PSEN1小鼠的学习、记忆和认知功能，其中增强的溶酶体降解能力促进淀粉样蛋白聚集体的清除。综上所述，本研究报道了神经转运体介导的溶酶体生物发生的新机制，并表明DAT抑制可以缓解阿尔茨海默病的发病机制。
More than 55 million people are suffering from Alzheimer's disease (AD), but there is still no effective treatment for it. Therefore, novel therapeutic approaches and regulatory mechanisms of protein quality control need to be further evaluated and dissected. The lysosome is one of the major degradative organelles that maintain cellular homeostasis and protein quality control. In our recent study, we have identified a group of LYsosome-Enhancing Compounds (LYECs), which significantly promote the activation of TFEB (transcription factor EB) and lysosome biogenesis via inhibiting dopamine transporters (DAT). Injection of LH2-051, a member of the LYECs identified in this study, significantly improves learning, memory, and cognitive function of APP-PSEN1 mice, in which the enhanced capability of lysosomal degradation promotes the clearance of amyloid protein aggregates. In summary, this study reports novel mechanisms of neurotransporter-mediated lysosome biogenesis and shows that DAT inhibition can alleviate the pathogenesis of Alzheimer's disease.
抑制多巴胺转运蛋白可促进溶酶体生物发生并改善小鼠的阿尔茨海默病样症状。
影响因子：
14
作者：
Yin, Limin;Zhou, Jianhui;Li, Yang
通讯作者：
Li, Yang