| Literature DB >> 29590078 |
Dena S Leeman1,2, Katja Hebestreit1, Tyson Ruetz1, Ashley E Webb1, Andrew McKay1,3, Elizabeth A Pollina1,2, Ben W Dulken1,4, Xiaoai Zhao1, Robin W Yeo1, Theodore T Ho5, Salah Mahmoudi1, Keerthana Devarajan1, Emmanuelle Passegué5, Thomas A Rando6,7, Judith Frydman1,8, Anne Brunet9,2,7.
Abstract
In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.Entities:
Mesh:
Year: 2018 PMID: 29590078 PMCID: PMC5915358 DOI: 10.1126/science.aag3048
Source DB: PubMed Journal: Science ISSN: 0036-8075 Impact factor: 47.728