Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging.
Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging.
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DOI：
10.1126/science.aag3048
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发表时间：
2018-03-16
期刊：
影响因子：
--
通讯作者：
Brunet A
中科院分区：
文献类型：
--
作者：
Leeman DS;Hebestreit K;Ruetz T;Webb AE;McKay A;Pollina EA;Dulken BW;Zhao X;Yeo RW;Ho TT;Mahmoudi S;Devarajan K;Passegué E;Rando TA;Frydman J;Brunet A
在成人脑中，神经干细胞（NSC）库包括具有不同作用的静止和活化群体。转录组学分析显示，静止和活化的神经干细胞在其蛋白质稳态网络中表现出差异。而活化的神经干细胞有活性的蛋白酶体，静止的神经干细胞含有大的溶酶体。来自年轻小鼠的静止神经干细胞积累蛋白质聚集体，并且这些聚集体中的许多储存在大的溶酶体中。静止神经干细胞中溶酶体活性的扰动影响蛋白聚集体的积累和静止神经干细胞的激活能力。在老化过程中，静止的神经干细胞显示其溶酶体缺陷，增加蛋白质聚集体的积累，并降低激活能力。在老的静止的NSC中增强溶酶体途径清除蛋白质聚集体并改善静止的NSC的活化能力，使它们恢复更年轻的状态。
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.
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影响因子：
6.1
作者：
Kernie SG;Parent JM
通讯作者：
Parent JM
影响因子：
29
作者：
Brandhorst S;Choi IY;Wei M;Cheng CW;Sedrakyan S;Navarrete G;Dubeau L;Yap LP;Park R;Vinciguerra M;Di Biase S;Mirzaei H;Mirisola MG;Childress P;Ji L;Groshen S;Penna F;Odetti P;Perin L;Conti PS;Ikeno Y;Kennedy BK;Cohen P;Morgan TE;Dorff TB;Longo VD
通讯作者：
Longo VD
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
DOI：
10.1126/science.aag2553
发表时间：
2017-06-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Di Malta C;Siciliano D;Calcagni A;Monfregola J;Punzi S;Pastore N;Eastes AN;Davis O;De Cegli R;Zampelli A;Di Giovannantonio LG;Nusco E;Platt N;Guida A;Ogmundsdottir MH;Lanfrancone L;Perera RM;Zoncu R;Pelicci PG;Settembre C;Ballabio A
通讯作者：
Ballabio A
影响因子：
64.8
作者：
Garcia-Prat, Laura;Martinez-Vicente, Marta;Munoz-Canoves, Pura
通讯作者：
Munoz-Canoves, Pura