Protein homeostasis and aging in neurodegeneration.

Protein homeostasis and aging in neurodegeneration.
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DOI:
10.1083/jcb.201005144
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发表时间:
2010-09-06
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Dillin A
Dillin A
中科院分区:
其他
文献类型:
--
作者:
Douglas PM;Dillin A

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导致许多神经退行性疾病的遗传和环境因素因疾病而异,但年龄仍然是一个普遍的风险因素。随着年龄的增长,蛋白质稳态或蛋白质稳态的下降,使与疾病相关的蛋白质采用异常的三级结构,以更高有序的聚集体形式积累,并导致无数细胞功能障碍和神经元死亡。然而,最近的发现表明,将疾病蛋白组装成紧密有序的聚集体可以显著推迟蛋白毒素的开始。此外,通过关键信号成分操纵代谢途径可以延长寿命,支持蛋白平衡网络,并延缓蛋白毒性的发生。因此,了解蛋白质平衡和衰老之间的关系为神经退行性变提供了重要的见解。
Genetic and environmental factors responsible for numerous neurodegenerative diseases vary between disorders, yet age remains a universal risk factor. Age-associated decline in protein homeostasis, or proteostasis, enables disease-linked proteins to adopt aberrant tertiary structures, accumulate as higher-ordered aggregates, and cause a myriad of cellular dysfunctions and neuronal death. However, recent findings suggest that the assembly of disease proteins into tightly ordered aggregates can significantly delay proteotoxic onset. Furthermore, manipulation of metabolic pathways through key signaling components extends lifespan, bolsters proteostasis networks, and delays the onset of proteotoxicity. Thus, understanding the relationship between proteostasis and aging has provided important insights into neurodegeneration.
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影响因子: --
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