Rezaeian Niloofar, Shirvanizadeh Niloofar, Mohammadi Soheila, Nikkhah Maryam, Arab Seyed Shahriar
Department of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Arch Biochem Biophys. 2017 Nov 15;634:96-106. doi: 10.1016/j.abb.2017.09.015. Epub 2017 Sep 28.
Parkinson's disease is characterized by accumulation of inclusion bodies in dopaminergic neurons, where insoluble and fibrillar α-synuclein makes up the major component of these inclusion bodies. So far, several strategies have been applied in order to suppress α-synuclein aggregation and toxicity in Parkinson's disease. In the present study, a new database has been established by segmentation of all the proteins deposited in protein Data Bank. The database data base was searched for the sequences which adopt β structure and are identical or very similar to the regions of α-synuclein which are involved in aggregation. The adjacent β strands of the found sequences were chosen as the peptide inhibitors of α-synuclein aggregation. Two of the predicted peptides, namely KISVRV and GQTYVLPG, were experimentally proved to be efficient in suppressing aggregation of α-synuclein in vitro. Moreover, KISVRV exhibited the ability to disrupt oligomers of α-syn which are assumed to be the pathogenic species in Parkinson's disease.
帕金森病的特征是多巴胺能神经元中包涵体的积累，其中不溶性和纤维状的α-突触核蛋白构成了这些包涵体的主要成分。到目前为止，已经应用了几种策略来抑制帕金森病中α-突触核蛋白的聚集和毒性。在本研究中，通过对蛋白质数据库中所有蛋白质进行分割建立了一个新的数据库。在该数据库中搜索采用β结构且与α-突触核蛋白参与聚集的区域相同或非常相似的序列。所发现序列的相邻β链被选作α-突触核蛋白聚集的肽抑制剂。实验证明，预测的两种肽，即KISVRV和GQTYVLPG，在体外能够有效抑制α-突触核蛋白的聚集。此外，KISVRV表现出破坏α-突触核蛋白寡聚体的能力，而这些寡聚体被认为是帕金森病中的致病物质。
