Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly.
Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly.
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DOI：
10.1038/s41467-022-29724-4
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发表时间：
2022-04-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
帕金森病（PD）是一种进行性神经退行性疾病，目前尚无成功的预防或干预措施。帕金森病的病理特征包括功能性α-突触核蛋白（αS）自组装为无功能的淀粉样结构。针对帕金森病的一种潜在治疗干预措施是有效抑制αS聚集。然而，实现这一目标的瓶颈在于识别对聚集至关重要的αS结构域/序列。通过一种蛋白质模拟方法，我们已经确定了基于αS序列的对聚集至关重要的靶点，这将具有重大的治疗意义。我们利用了大量的体外、离体和体内实验来验证对帕金森病表型的聚集和传播至关重要的αS序列及其结构特征。这项研究有助于深入了解αS聚集的各个方面的机制和治疗方法，这将为帕金森病的有效治疗铺平道路。
抑制α-突触核蛋白自组装为与帕金森病相关的淀粉样结构是一种潜在的治疗干预措施。在这里，作者确定了对α-突触核蛋白聚集至关重要的结构域/序列，并测试了基于折叠体的拮抗剂的活性以确定潜在的治疗靶点。
Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays is utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for effective treatments for PD. Inhibiting alpha-synuclein self-assembly into amyloid structures, associated with Parkinson’s disease, is a potential therapeutic intervention. Here, the authors identify the domains/sequences that are essential for alpha-synuclein aggregation and test the activity of foldamer-based antagonists to identify potential therapeutic targets.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
Lee, VMY
影响因子：
21.8
作者：
Chandramouli, Nagula;Ferrand, Yann;Huc, Ivan
通讯作者：
Huc, Ivan
影响因子：
7.7
作者：
Agerschou, Emil Dandanell;Flagmeier, Patrick;Buell, Alexander K.
通讯作者：
Buell, Alexander K.
DOI：
10.1007/978-1-61779-551-0_14
发表时间：
2012-01-01
期刊：
AMYLOID PROTEINS: METHODS AND PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Barria, Marcelo A.;Gonzalez-Romero, Dennisse;Soto, Claudio
通讯作者：
Soto, Claudio
影响因子：
16.6
作者：
Bousset, Luc;Pieri, Laura;Melki, Ronald
通讯作者：
Melki, Ronald