The yeast stress inducible Ssa Hsp70 reduces α-synuclein toxicity by promoting its degradation through autophagy.
The yeast stress inducible Ssa Hsp70 reduces α-synuclein toxicity by promoting its degradation through autophagy.
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DOI：
10.1371/journal.pgen.1007751
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发表时间：
2018-10
期刊：
影响因子：
4.5
通讯作者：
Sharma D
中科院分区：
文献类型：
--
作者：
Gupta A;Puri A;Singh P;Sonam S;Pandey R;Sharma D
Hsp 70在与细胞内毒性蛋白内含物积累相关的毒性中的作用机制正在深入研究中。在本研究中，我们研究了酵母胞浆Ssa Hsp 70的所有不同亚型在α-synuclein介导的细胞毒性中的作用。研究表明，表达应激诱导型Ssa 3或Ssa 4作为唯一Ssa Hsp 70同种型的酵母细胞比表达组成型对应物的酵母细胞更好地降低α-突触核蛋白毒性。胁迫诱导的Ssa Hsp 70 s的保护作用不是α-syn特异性的，而是对其他包含体形成蛋白如polyQ更普遍的。我们表明，保护作用不是通过诱导Ssa 3细胞中的一般应激反应，而是通过自噬促进α-突触核蛋白降解。目前的研究表明，热休克蛋白70 s的影响是异构体依赖性的，自噬保护Ssa 3细胞免受有毒蛋白夹杂物的有害影响。蛋白质内含物的积累是许多神经退行性疾病的共同特征。Hsp 70分子伴侣已经成为由蛋白质内含物（例如由α-突触核蛋白和polyQ形成的蛋白质内含物）引起的毒性的有效抑制剂。Hsp 70介导的作用的潜在机制仍不清楚，并且据信Hsp 70的抗聚集活性降低了蛋白包含物介导的毒性。在本研究中，我们研究了酵母胞质Ssa Hsp 70家族伴侣蛋白在α-突触核蛋白介导的毒性中的作用。我们表明，应激诱导型Ssa Hsp 70比其组成型对应物更好地保护细胞免受α-突触核蛋白和polyQ毒性。我们的研究揭示了应激诱导的Hsp 70在自噬介导的α-synuclein降解中的作用保护细胞免受α-synuclein介导的毒性。
The mechanism underlying the role of Hsp70s in toxicity associated with intracellular accumulation of toxic protein inclusions is under intense investigation. In current study, we examined the roles of all different isoforms of yeast cytosolic Ssa Hsp70 on α-synuclein mediated cellular toxicity. The study showed that yeast cells expressing stress-inducible Ssa3 or Ssa4 as sole Ssa Hsp70 isoforms, reduced α-synuclein toxicity better than those expressing a constitutive counterpart. The protective effect of stress-inducible Ssa Hsp70s was not α-syn specific, but more general to other inclusion forming proteins such as polyQ. We show that the protective effect is not by induction of a general stress response in Ssa3 cells rather by promoting α-synuclein degradation through autophagy. The present study revealed that effect of Hsp70s was isoform dependent, and that autophagy protects Ssa3 cells from the deleterious effects of toxic protein inclusions. The accumulation of protein inclusions is a common feature in many neurodegenerative diseases. The Hsp70 chaperones has emerged as potent suppressor of toxicity caused by protein inclusions such as those formed of α-synuclein and polyQ. The underlying mechanism of Hsp70 mediated effect remains unclear, and it is believed that anti-aggregation activity of Hsp70 reduces protein inclusion mediated toxicity. In the present study, we examined the role of yeast cytosolic Ssa Hsp70 family of chaperones on α-synuclein mediated toxicity. We show that stress inducible Ssa Hsp70s are better than their constitutive counterparts to protect cells from both α-synuclein and polyQ toxicity. Our study reveals that the role of stress inducible Hsp70 in autophagy mediated degradation of α-synuclein protect cells from α-synuclein mediated toxicity.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
将果糖-1, 6-双磷酸酶导入 Vid 囊泡需要热休克蛋白 Ssa2p。
DOI：
10.1083/jcb.150.1.65
发表时间：
2000-07-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
5.1
作者：
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通讯作者：
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影响因子：
3.2
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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