热休克蛋白70（Hsc70）蛋白与纤维状α-突触核蛋白的相互作用及其在帕金森病中的治疗潜力。
The interaction of Hsc70 protein with fibrillar α-Synuclein and its therapeutic potential in Parkinson's disease.
作者信息
Pemberton Samantha, Melki Ronald
机构信息
Laboratoire d'Enzymologie et Biochimie Structurales; CNRS; Gif-sur-Yvette, France.
出版信息
Commun Integr Biol. 2012 Jan 1;5(1):94-5. doi: 10.4161/cib.18483.
Abstract
We recently described the effect of the constitutively expressed chaperone, Hsc70 protein, on α‑Synuclein aggregation, a phenomenon associated with Parkinson disease. In vitro, Hsc70 binds to soluble α‑Syn and slows down its assembly into fibrils. Hsc70 also binds fibrillar α‑Syn, 5-fold tighter than soluble α‑Syn. This interaction reduces the cytotoxicity associated with naked α‑Syn fibrils. Herein, we discuss the feasibility of engineering a "minichaperone" which could be used against α‑Syn assembly propagation in Parkinson disease: taking what is necessary and sufficient within Hsc70 to protect against the damaging repercussions of high molecular weight α‑Syn species' passage from one neuron to another in the brain.
摘要
我们最近描述了组成型表达的伴侣蛋白Hsc70对α-突触核蛋白聚集的影响，这是一种与帕金森病相关的现象。在体外，Hsc70与可溶性α-突触核蛋白结合，并减缓其组装成纤维的过程。Hsc70还与纤维状α-突触核蛋白结合，其结合力比可溶性α-突触核蛋白强5倍。这种相互作用降低了与裸露的α-突触核蛋白纤维相关的细胞毒性。在此，我们讨论了设计一种“微型伴侣蛋白”的可行性，该蛋白可用于对抗帕金森病中α-突触核蛋白组装的传播：即利用Hsc70中必要且充分的部分来防止高分子量α-突触核蛋白在大脑中从一个神经元传递到另一个神经元所产生的有害影响。
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