Alpha-synuclein and chaperones in dementia with Lewy bodies
Alpha-synuclein and chaperones in dementia with Lewy bodies
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DOI：
10.1097/01.jnen.0000190063.90440.69
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发表时间：
2005-12-01
影响因子：
3.2
通讯作者：
Standaert, DG
中科院分区：
文献类型：
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作者：
Cantuti-Castelvetri, I;Klucken, J;Standaert, DG
α-突触核蛋白(ASYN)被认为与路易体痴呆(DLB)的发生有关。ASYN的过度表达与细胞毒性和人类疾病有关，在实验模型中，热休克蛋白(HSPs)等伴侣蛋白对ASYN毒性具有保护作用。我们评估了散发性人类DLB患者颞叶皮质中ASYN和伴侣蛋白mRNA的丰度以及编码蛋白的丰度和可溶性。我们发现DLB的ASYN基因表达减少(44.9%)。Triton可溶部分(生物可用蛋白)的丰度没有改变，但Triton-in可溶部分(可能代表聚集体)的丰度增加。我们评估了3个伴侣：HSP70、HSP90和HDJ1。DLBHSP70mRNA表达增加，而HSP90和HDJ1mRNAs无明显变化。HSP70在Triton可溶组分中积累，而HSP90和HDJ1蛋白在Triton不溶组分中积累。这些观察结果表明，散发性DLB与ASYN的过度表达无关。相反，尽管其mRNA减少，但正常的可溶性ASYN蛋白水平的持续存在，表明该蛋白的清除存在初级缺陷。然而，这种清除能力的降低不能归因于伴侣蛋白表达的失败，因为它们在DLB脑中的mRNA没有改变或增加。
The protein alpha-synuclein (ASYN) is thought to be involved in the development of dementia with Lewy bodies (DLB). Overexpression of ASYN has been linked to cellular toxicity and human disease, and in experimental models, chaperones such as heat shock proteins (HSPs) are protective against ASYN toxicity We have assessed the abundance of mRNA for ASYN and chaperones and the abundance and solubility of the encoded proteins in temporal cortex from sporadic human DLB. We found a reduction of ASYN mRNA in DLB (44.9% of control). The abundance of the Triton-soluble fraction (bioavailable protein) was not altered, but there was an increase of the Triton-in soluble component (likely representing aggregates). We evaluated 3 chaperones: HSP70, HSP90, and HDJ1. HSP70 mRNA was increased in DLB, whereas the mRNAs for HSP90 and HDJ1 were unchanged. HSP70 accumulated in the Triton-soluble fraction, whereas HSP90 and HDJ1 proteins accumulated in the Triton-insoluble fraction. These observations suggest that sporadic DLB is not associated with overexpression of ASYN. Rather, the persistence of normal soluble ASYN protein levels, despite the reduction of its mRNA, suggests a primary defect in clearance of the protein. However, this reduced clearance cannot be attributed to a failure of chaperone expression, because their mRNA is unchanged or increased in the DLB brain.