title: Essential role of proteasomes in maintaining self-renewal in neural progenitor cells.
abstract: 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 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.
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Physiology, East Carolina University Medical School, Greenville, 27834, USA.
authors.forename: Jian M
authors.initials: JM
authors.lastname: Ding
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.|Guangdong Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 510632, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Psychology, Nanjing Normal University, Nanjing, 210097, China.
authors.forename: Tifei
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.|Guangdong Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 510632, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.|Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
authors.forename: Wulin
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
mesh_terms: D000375:Aging; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D016922:Cellular Senescence; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D046988:Proteasome Endopeptidase Complex