Essential role of proteasomes in maintaining self-renewal in neural progenitor cells

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Yunhe,Liu,Xueqin,He,Zebin,Niu,Xiaojie,Shi,Weijun,D M.,Zhang,Li,Yuan,Tifei,Li,Ang,Yang,Wulin,Lu,Li Zhao (Creator)
East Carolina University (ECU )
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Abstract: Protein turnover and homeostasis are regulated by the proteasomal system, which is critical forcell function and viability. Pluripotency of stem cells also relies on normal proteasomal activity that mitigates senescent phenotypes induced by intensive cell replications, as previously demonstratedin human bone marrow stromal cells. In this study, we investigated the role of proteasomes in self- renewal of neural progenitor cells (NPCs). Through both in vivo and in vitro analyses, we found that the expression of proteasomes was progressively decreased during aging. Likewise, proliferation and self- renewal of NPCs were also impaired in aged mice, suggesting that the down-regulation of proteasomes might be responsible for this senescent phenotype. Lowering proteasomal activity by loss-of-function manipulations mimicked the senescence of NPCs both in vitro and in vivo; conversely, enhancing proteasomal activity restored and improved self-renewal in aged NPCs. These results collectively indicate that proteasomes work as a key regulator in promoting self-renewal of NPCs. This potentially provides a promising therapeutic target for age-dependent neurodegenerative diseases.

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Language: English
Date: 2016

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