Yoo Je Min, Lin Yuxi, Heo Yunseok, Lee Young-Ho
BioGraphene Inc, Los Angeles, CA, United States.
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang, South Korea.
Front Mol Biosci. 2022 Aug 12;9:959425. doi: 10.3389/fmolb.2022.959425. eCollection 2022.
The major hallmark of Parkinson's disease (PD) is represented by the formation of pathological protein plaques largely consisting of α-synuclein (αSN) amyloid fibrils. Nevertheless, the implications of αSN oligomers in neuronal impairments and disease progression are more importantly highlighted than mature fibrils, as they provoke more detrimental damages in neuronal cells and thereby exacerbate α-synucleinopathy. Interestingly, although generation of oligomeric species under disease conditions is likely correlated to cytotoxicity and different cellular damages, αSN oligomers manifest varying toxicity profiles dependent on the specific environments as well as the shapes and conformations the oligomers adopt. As such, this minireview discusses polymorphism in αSN oligomers and the association of the underlying heterogeneity in regard to toxicity under pathological conditions.
帕金森病（PD）的主要标志是形成主要由α-突触核蛋白（αSN）淀粉样原纤维组成的病理性蛋白质斑块。然而，αSN寡聚体在神经元损伤和疾病进展中的影响比成熟原纤维更受关注，因为它们在神经元细胞中引发更有害的损伤，从而加剧α-突触核蛋白病。有趣的是，尽管在疾病条件下寡聚体的产生可能与细胞毒性和不同的细胞损伤相关，但αSN寡聚体表现出不同的毒性特征，这取决于特定的环境以及寡聚体所采用的形状和构象。因此，本综述讨论了αSN寡聚体的多态性以及病理条件下潜在异质性与毒性的关联。
