Department of Chemistry, Renmin University of China, Beijing, 100872, P. R. China.
Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202111853. doi: 10.1002/anie.202111853. Epub 2021 Nov 22.
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.
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。
