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维生素 D 抑制α-突触核蛋白的早期聚集并通过电化学测量调节胞吐作用。

Vitamin D Inhibits the Early Aggregation of α-Synuclein and Modulates Exocytosis Revealed by Electrochemical Measurements.

机构信息

Department of Chemistry, Renmin University of China, Beijing, 100872, P. R. China.

出版信息

Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202111853. doi: 10.1002/anie.202111853. Epub 2021 Nov 22.

Abstract

Alpha-synuclein (α-Syn) localizes at presynaptic terminal and modulates synaptic functions. Increasing evidence demonstrate that α-Syn oligomers, forming at the early of aggregation, are cytotoxic and is thus related to brain neurodegenerative diseases. Herein, we find that vitamin D (VD) can reduce neurocytotoxicity. The reduced neurocytotoxicity might be attributed to the less amount of large-sized α-Syn oligomers inhibited by VD, measured by electrochemical collision at single particle level, which are not observable with traditionally ensembled method. Single-cell amperometry (SCA) results show that VD can recover the amount of neurotransmitter release during exocytosis induced by α-Syn oligomers, further verifying the neuroprotection of VD. Our study reveals the neuroprotective role of VD through inhibiting α-Syn aggregation, which is envisioned to be of great importance in treatment and prevention of the neurodegenerative diseases.

摘要

α-突触核蛋白(α-Syn)定位于突触前末梢,调节突触功能。越来越多的证据表明,在聚集的早期形成的α-Syn 寡聚物具有细胞毒性,因此与脑神经退行性疾病有关。在此,我们发现维生素 D(VD)可以降低神经细胞毒性。VD 降低神经细胞毒性可能归因于电化学碰撞在单颗粒水平上测量的、由 VD 抑制的大型 α-Syn 寡聚物数量减少,而传统的集合方法则无法观察到。单细胞安培法(SCA)结果表明,VD 可以恢复 α-Syn 寡聚物诱导的胞吐作用期间神经递质释放的量,进一步验证了 VD 的神经保护作用。我们的研究通过抑制 α-Syn 聚集揭示了 VD 的神经保护作用,这对于治疗和预防神经退行性疾病具有重要意义。

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