A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease.
A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease.
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DOI：
10.1016/j.celrep.2014.09.042
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发表时间：
2014-11-06
期刊：
影响因子：
8.8
通讯作者：
Morimoto RI
中科院分区：
文献类型：
--
作者：
Brehme M;Voisine C;Rolland T;Wachi S;Soper JH;Zhu Y;Orton K;Villella A;Garza D;Vidal M;Ge H;Morimoto RI
分子伴侣是蛋白质稳定网络（PN）的核心，保护蛋白质组免于错误折叠、聚集和蛋白毒性。我们使用功能，定位，相互作用组和表达数据集将332个基因的人类伴侣蛋白组分类为网络社区。在人脑衰老过程中，32%的伴侣蛋白组对应于ATP依赖性伴侣机器的表达被抑制，而19.5%对应于ATP非依赖性伴侣蛋白和辅助伴侣蛋白的表达被诱导。这些抑制和诱导簇在阿尔茨海默氏症、亨廷顿氏症和帕金森氏症的大脑中得到增强。通过C. elegans和表达Aβ、多聚谷氨酰胺和亨廷顿蛋白的人细胞模型。在219摄氏度。elegans直系同源物中，敲低16个增强了Aβ和polyQ相关的毒性。这些对应于28个人类直系同源物，其中52%和41%分别在脑老化和疾病中被抑制，37.5%影响人类细胞中的亨廷顿蛋白聚集。这些结果确定了在衰老和疾病中起作用的关键伴侣子网络。
Chaperones are central to the proteostasis network (PN) and safeguard the proteome from misfolding, aggregation and proteotoxicity. We categorized the human chaperome of 332 genes into network communities using function, localization, interactome, and expression datasets. During human brain aging, expression of 32% of the chaperome corresponding to ATP-dependent chaperone machines is repressed, whereas 19.5% corresponding to ATP-independent chaperones and co-chaperones are induced. These repression and induction clusters are enhanced in Alzheimer's, Huntington's, and Parkinson's brains. Functional properties of the chaperome were assessed by perturbation in C. elegans and human cell models expressing Aβ, polyglutamine and Huntingtin. Of 219 C. elegans orthologs, knockdown of sixteen enhanced both Aβ and polyQ-associated toxicity. These correspond to 28 human orthologs, of which 52% and 41% are repressed, respectively, in brain aging and disease, and 37.5% affected Huntingtin aggregation in human cells. These results identify a critical chaperome sub-network that functions in aging and disease.
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影响因子：
14.9
作者：
Hunter S;Jones P;Mitchell A;Apweiler R;Attwood TK;Bateman A;Bernard T;Binns D;Bork P;Burge S;de Castro E;Coggill P;Corbett M;Das U;Daugherty L;Duquenne L;Finn RD;Fraser M;Gough J;Haft D;Hulo N;Kahn D;Kelly E;Letunic I;Lonsdale D;Lopez R;Madera M;Maslen J;McAnulla C;McDowall J;McMenamin C;Mi H;Mutowo-Muellenet P;Mulder N;Natale D;Orengo C;Pesseat S;Punta M;Quinn AF;Rivoire C;Sangrador-Vegas A;Selengut JD;Sigrist CJ;Scheremetjew M;Tate J;Thimmajanarthanan M;Thomas PD;Wu CH;Yeats C;Yong SY
通讯作者：
Yong SY
影响因子：
64.5
作者：
Albanèse, V;Yam, AYW;Frydman, J
通讯作者：
Frydman, J
影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G
影响因子：
5.3
作者：
Almeida, A;Bolaños, JP;Moreno, S
通讯作者：
Moreno, S
影响因子：
120.1
作者：
Ehrnhoefer, Dagmar E.;Wong, Bibiana K. Y.;Hayden, Michael R.
通讯作者：
Hayden, Michael R.