Medical Genetics and Neurogenetics Unit - Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
Section of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Biochim Biophys Acta Mol Cell Res. 2024 Dec;1871(8):119842. doi: 10.1016/j.bbamcr.2024.119842. Epub 2024 Sep 13.
De novo mutations in the WDR45 gene have been found in patients affected by Neurodegeneration with Brain Iron Accumulation type 5 (NBIA5 or BPAN), with Non-Transferrin Bound Iron (NTBI) accumulation in the basal ganglia and WDR45-dependent impairment of autophagy. Here we show the downregulation of TFEB and cell cycle impairment in BPAN primary fibroblasts. Noteworthy, TFEB overexpression rescued this impairment, depicting a novel WDR45-dependent cell cycle phenotype.
在患有神经退行性脑铁蓄积症 5 型（NBIA5 或 BPAN）的患者中发现了 WDR45 基因的新生突变，其特征是基底节中非转铁蛋白结合铁（NTBI）的积累和 WDR45 依赖性自噬受损。在这里，我们显示了 BPAN 原代成纤维细胞中 TFEB 的下调和细胞周期受损。值得注意的是，TFEB 的过表达挽救了这种损伤，描绘了一种新的 WDR45 依赖性细胞周期表型。
