Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity

Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity

Senolytics have the potential to extend healthspan by selectively killing senescent cells (SCs), but senolytics that target Bcl-xl may cause platelet toxicity. Here, the authors generated a Bcl-xl proteolysis-targeting chimera (PROTAC) senolytic, which effectively clears SCs and rejuvenates tissue s...

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Autores principales: Yonghan He, Xuan Zhang, Jianhui Chang, Ha-Neui Kim, Peiyi Zhang, Yingying Wang, Sajid Khan, Xingui Liu, Xin Zhang, Dongwen Lv, Lin Song, Wen Li, Dinesh Thummuri, Yaxia Yuan, Janet S. Wiegand, Yuma T. Ortiz, Vivekananda Budamagunta, Jennifer H. Elisseeff, Judith Campisi, Maria Almeida, Guangrong Zheng, Daohong Zhou
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
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Science
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Acceso en línea:https://doaj.org/article/dc8e747a1c2b46fbb1cf6eb91566a85f
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Sumario:Senolytics have the potential to extend healthspan by selectively killing senescent cells (SCs), but senolytics that target Bcl-xl may cause platelet toxicity. Here, the authors generated a Bcl-xl proteolysis-targeting chimera (PROTAC) senolytic, which effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia.

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