Essential role of proteasomes in maintaining self-renewal in neural progenitor cells.
Essential role of proteasomes in maintaining self-renewal in neural progenitor cells.
复制标题
蛋白酶体在维持神经祖细胞自我更新中的重要作用
DOI：
10.1038/srep19752
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发表时间：
2016-01-25
影响因子：
4.6
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Zhao Y;Liu X;He Z;Niu X;Shi W;Ding JM;Zhang L;Yuan T;Li A;Yang W;Lu L
蛋白质周转和动态平衡是由蛋白酶体系统调节的，蛋白酶体系统对细胞功能和活性至关重要。干细胞的多能性还依赖于正常的蛋白酶体活性，这种活性可以减轻由密集细胞复制引起的衰老表型，就像之前在人类骨髓基质细胞中所证明的那样。在这项研究中，我们研究了蛋白酶体在神经前体细胞自我更新中的作用。通过活体蛋白体外分析，我们发现随着年龄的增长，蛋白酶体的表达逐渐减少。同样，在衰老小鼠中，NPC的增殖和自我更新也受到损害，这表明蛋白酶体的下调可能是这种衰老表型的原因。通过功能丧失降低蛋白酶体活性可以模拟神经干细胞在体外和体内的衰老过程；相反，增强蛋白酶体活性可以恢复和改善老年神经干细胞的自我更新。这些结果共同表明，蛋白酶体在促进鼻咽癌细胞自我更新方面起着关键的调节作用。这可能为年龄依赖性神经退行性疾病提供一个有希望的治疗靶点。
Protein turnover and homeostasis are regulated by the proteasomal system, which is critical for cell function and viability. Pluripotency of stem cells also relies on normal proteasomal activity that mitigates senescent phenotypes induced by intensive cell replications, as previously demonstrated in human bone marrow stromal cells. In this study, we investigated the role of proteasomes in self-renewal of neural progenitor cells (NPCs). Through bothin vivoandin vitroanalyses, 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 bothin vitroandin 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.