Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
Neuroscience Center, Helsinki University, Helsinki, Finland.
Bull Exp Biol Med. 2022 Apr;172(6):785-788. doi: 10.1007/s10517-022-05478-3. Epub 2022 May 3.
Mutations in the PSEN1 gene encoding presenilin-1 (PS1) protein are the most common cause of familial Alzheimer's disease. One of these, deletion of exon 9, results in the production of shortened PS1 protein (PS1ΔE9). Neuronal hyperexcitability and hyperactivation of L-type calcium channels were observed in cellular and animal models of familial Alzheimer's disease. However, the effect of PS1ΔE9 on L-type calcium channels has not been studied before. We demonstrate enhanced calcium entry through L-type calcium channels in hippocampal mouse neurons with exogenous expression of PS1ΔE9. Additionally, we show that the same effect of the exogenous PS1ΔE9 can be observed in cells with predominant expression of L-type calcium channels subunit Cav1.2. Further research is required to unravel molecular mechanisms underlying hyperactivation L-type calcium channels caused by PS1ΔE9 expression.
编码早老素-1（PS1）蛋白的 PSEN1 基因突变是家族性阿尔茨海默病最常见的原因之一。其中之一是外显子 9 的缺失，导致产生缩短的 PS1 蛋白（PS1ΔE9）。在家族性阿尔茨海默病的细胞和动物模型中观察到神经元过度兴奋和 L 型钙通道过度激活。然而，PS1ΔE9 对 L 型钙通道的影响以前尚未研究过。我们证明在海马小鼠神经元中外源表达 PS1ΔE9 可增强钙内流通过 L 型钙通道。此外，我们还表明，在主要表达 L 型钙通道亚基 Cav1.2 的细胞中也可以观察到外源性 PS1ΔE9 的相同作用。需要进一步研究来阐明 PS1ΔE9 表达引起的 L 型钙通道过度激活的分子机制。
