Observation of α-Synuclein Preformed Fibrils Interacting with SH-SY5Y Neuroblastoma Cell Membranes Using Scanning Ion Conductance Microscopy.
Observation of α-Synuclein Preformed Fibrils Interacting with SH-SY5Y Neuroblastoma Cell Membranes Using Scanning Ion Conductance Microscopy.
复制标题
DOI：
10.1021/acschemneuro.2c00478
复制
发表时间：
2022-12-21
影响因子：
5
通讯作者：
Wang, Yixian
中科院分区：
文献类型：
--
作者：
Feng, Christina;Flores, Marisol;Dhoj, Christina;Garcia, Adaly;Belleca, Sheehan;Abou Abbas, Dana;Parres-Gold, Jacob;Anguiano, Aimee;Porter, Edith;Wang, Yixian
帕金森病(PD)是美国第二常见的神经退行性疾病。α-突触核蛋白(α-Syn)预形成的纤维(PFF)已被证明在神经元群体中传播帕金森病的病理。然而，很少有工作直接在细胞水平上表征与α-Syn pff相关的膜的形态变化。扫描离子电导显微镜(SICM)是一种非侵入性的原位细胞成像技术，因此在研究PFF诱导的神经母细胞瘤细胞膜变化方面具有独特的优势。本工作用免疫印迹技术检测了不同浓度的α-Syn pff作用于SH-SY5Y神经母细胞瘤细胞后细胞膜的变化。细胞膜粗糙度随α-Syn pff浓度的增加而显著增加。在较高的α-Syn PFF浓度下，也观察到了明显的突起，呈现出更多的结晶外观。细胞存活率仅略有下降，但在统计学上有显著意义，降至约80%，但与剂量无关。这些观察表明，在48小时的处理期间，PFF继续在细胞膜上积累，导致膜粗糙度增加，而不会导致显著的细胞死亡。由于PFF不会导致主要细胞死亡，这些数据表明，在进一步聚集之前针对纤维的早期干预可能会阻止帕金森病神经元丢失的进展。
Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder in the U.S. α-Synuclein (α-Syn) preformed fibrils (PFFs) have been shown to propagate PD pathology in neuronal populations. However, little work has directly characterized the morphological changes on membranes associated with α-Syn PFFs at a cellular level. Scanning ion conductance microscopy (SICM) is a noninvasive in situ cell imaging technique and therefore uniquely advantageous to investigate PFF-induced membrane changes in neuroblastoma cells. The present work used SICM to monitor cytoplasmic membrane changes of SH-SY5Y neuroblastoma cells after incubation with varying concentrations of α-Syn PFFs. Cell membrane roughness significantly increased as the concentration of α-Syn PFFs increased. Noticeable protrusions that assumed a more crystalline appearance at higher α-Syn PFF concentrations were also observed. Cell viability was only slightly reduced, though statistically significantly, to about 80% but independent of the dose. These observations indicate that within the 48 h treatment period, PFFs continue to accumulate on the cell membranes, leading to membrane roughness increase without causing prominent cell death. Since PFFs did not induce major cell death, these data suggest that early interventions targeting fibrils before further aggregation may prevent the progression of neuron loss in Parkinson’s disease.
登录
查看更多内容
影响因子：
16.6
作者：
Cascella R;Chen SW;Bigi A;Camino JD;Xu CK;Dobson CM;Chiti F;Cremades N;Cecchi C
通讯作者：
Cecchi C
DOI：
10.3390/life11050431
发表时间：
2021-05-11
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Bigi A;Ermini E;Chen SW;Cascella R;Cecchi C
通讯作者：
Cecchi C
影响因子：
2.4
作者：
Aulić S;Le TT;Moda F;Abounit S;Corvaglia S;Casalis L;Gustincich S;Zurzolo C;Tagliavini F;Legname G
通讯作者：
Legname G
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
5.3
作者：
Wu, Qihui;Takano, WHajime;Lee, Virginia M-Y
通讯作者：
Lee, Virginia M-Y