Designer protein disaggregases to counter neurodegenerative disease.
Designer protein disaggregases to counter neurodegenerative disease.
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DOI：
10.1016/j.gde.2017.01.008
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发表时间：
2017-06
影响因子：
4
通讯作者：
Shorter J
中科院分区：
文献类型：
--
作者：
Shorter J
蛋白质错误折叠和聚集导致了几种毁灭性的神经退行性疾病，包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。对于这些疾病没有有效的治疗方法，也没有针对逆转引起疾病的异常蛋白质错误折叠和聚集的方法。在这里，我展示了定义、设计和应用蛋白质解聚酶以减轻有害蛋白质错误折叠和对抗神经退行性变的重要进展。我重点研究两种外源蛋白解聚酶，来自酵母的 Hsp104 和来自噬菌体的基因 3 蛋白，以及内源性人类蛋白解聚酶，包括： (a) Hsp110、Hsp70、Hsp40 和小热休克蛋白； (b) HtrA1； (c) NMNAT2 和 Hsp90。我建议蛋白质解聚酶方式可以用于治疗许多致命且目前无法治愈的神经退行性疾病。
Protein misfolding and aggregation unify several devastating neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. There are no effective therapeutics for these disorders and none that target the reversal of the aberrant protein misfolding and aggregation that cause disease. Here, I showcase important advances to define, engineer, and apply protein disaggregases to mitigate deleterious protein misfolding and counter neurodegeneration. I focus on two exogenous protein disaggregases, Hsp104 from yeast and gene 3 protein from bacteriophages, as well as endogenous human protein disaggregases, including: (a) Hsp110, Hsp70, Hsp40, and small heat-shock proteins; (b) HtrA1; and (c) NMNAT2 and Hsp90. I suggest that protein-disaggregase modalities can be channeled to treat numerous fatal and presently incurable neurodegenerative diseases.