Multiplicity of α-Synuclein Aggregated Species and Their Possible Roles in Disease.
Multiplicity of α-Synuclein Aggregated Species and Their Possible Roles in Disease.
复制标题
α-突触核蛋白聚集体的多样性及其在疾病中的可能作用。
DOI：
10.3390/ijms21218043
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发表时间：
2020-10-28
影响因子：
5.6
通讯作者：
Cremades N
中科院分区：
文献类型：
--
作者：
Gracia P;Camino JD;Volpicelli-Daley L;Cremades N
α-突触核蛋白淀粉样蛋白聚集是帕金森病、路易体痴呆和多系统萎缩的定义性分子特征，但也可以在其他神经退行性疾病如阿尔茨海默病中发现。α-突触核蛋白聚集的过程可以通过替代的成核机制启动，并由不同的次级过程主导，产生多种淀粉样蛋白多晶型物和中间物质。一些聚集的物种具有更多的内在能力来诱导细胞应激和毒性，而其他物种似乎在传播神经变性方面更有效。对特定类型的多晶型的偏好取决于蛋白质遇到的溶液条件和细胞微环境，这可能与不同突触核蛋白病中α-突触核蛋白包涵体的不同细胞位置以及疾病特异性淀粉样蛋白多晶型的存在有关。在这篇综述中，我们讨论了我们目前对各种类型的α-突触核蛋白聚集物种的性质和结构及其在病理学中可能的作用的理解。精确定义这些不同的α-突触核蛋白种类将有助于理解这些疾病的分子起源，开发准确的诊断，并为这些高度衰弱的神经退行性疾病设计有效的治疗干预措施。
α-Synuclein amyloid aggregation is a defining molecular feature of Parkinson’s disease, Lewy body dementia, and multiple system atrophy, but can also be found in other neurodegenerative disorders such as Alzheimer’s disease. The process of α-synuclein aggregation can be initiated through alternative nucleation mechanisms and dominated by different secondary processes giving rise to multiple amyloid polymorphs and intermediate species. Some aggregated species have more inherent abilities to induce cellular stress and toxicity, while others seem to be more potent in propagating neurodegeneration. The preference for particular types of polymorphs depends on the solution conditions and the cellular microenvironment that the protein encounters, which is likely related to the distinct cellular locations of α-synuclein inclusions in different synucleinopathies, and the existence of disease-specific amyloid polymorphs. In this review, we discuss our current understanding on the nature and structure of the various types of α-synuclein aggregated species and their possible roles in pathology. Precisely defining these distinct α-synuclein species will contribute to understanding the molecular origins of these disorders, developing accurate diagnoses, and designing effective therapeutic interventions for these highly debilitating neurodegenerative diseases.
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影响因子：
8.6
作者：
Appel-Cresswell, Silke;Vilarino-Guell, Carles;Farrer, Matthew J.
通讯作者：
Farrer, Matthew J.
DOI：
10.1073/pnas.0407146102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Bertoncini, CW;Jung, YS;Zweckstetter, M
通讯作者：
Zweckstetter, M
影响因子：
4
作者：
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通讯作者：
Abramov AY
影响因子：
3.4
作者：
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通讯作者：
Beyer, Klaus
影响因子：
4.8
作者：
Babinchak, W. Michael;Haider, Raza;Surewicz, Witold K.
通讯作者：
Surewicz, Witold K.