Bellomi Francesco, Caturano Claudia, Velardi Viola, Mancinelli Romina, Carotti Simone, Vivacqua Giorgio, Arciprete Francesca, Zingariello Maria
Laboratory of Microscopic and Ultrastructural Anatomy, Campus Bio-Medico University of Roma, Roma, Italy.
Section of Human Anatomy, Department of Anatomic, Histologic, Forensic Medicine and Locomotor Apparatus Sciences, Sapienza University of Roma, Roma, Italy.
Dev Neurobiol. 2025 Jul;85(3):e22975. doi: 10.1002/dneu.22975.
Alpha-synuclein (α-syn), a 140 amino acid protein, is abundantly expressed in the central nervous system (CNS) and in the erythrocytes, playing a pivotal role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Among the GATA family transcription factors (TFs), GATA1 and GATA2 regulate the meg-erythrocytic differentiation starting from the hematopoietic stem cell. In erythropoiesis, the GATA1-2 switching regulates the expression of the α-syn gene (SNCA) in the erythrocytes, which is essential for iron metabolism and membrane stability. Abnormalities in α-syn regulation alter erythrocytic function, possibly contributing to pathological mechanisms of different synucleinopathies. In CNS, during neuronal development, GATA2 confirms its role in stemness by maintaining the ventral neuronal progenitors and also leading GABAergic, serotoninergic, and sympathetic neuron differentiation. Therefore, although no evidence is reported regarding a direct role of GATA1 in neuronal lineage, GATA3 recruitment and activation are essential for the maturation of specific neuronal subtypes. This short scope review explores the bridging role of GATA TFs in erythropoiesis and neuronal development, highlighting their involvement in α-syn regulation, as well as their potential role in the pathogenesis of synucleinopathies.
α-突触核蛋白（α-syn）是一种由140个氨基酸组成的蛋白质，在中枢神经系统（CNS）和红细胞中大量表达，在帕金森病（PD）和其他突触核蛋白病的发病机制中起关键作用。在GATA家族转录因子（TFs）中，GATA1和GATA2从造血干细胞开始调节巨红细胞分化。在红细胞生成过程中，GATA1-2转换调节红细胞中α-突触核蛋白基因（SNCA）的表达，这对铁代谢和膜稳定性至关重要。α-突触核蛋白调节异常会改变红细胞功能，可能导致不同突触核蛋白病的病理机制。在中枢神经系统中，在神经元发育过程中，GATA2通过维持腹侧神经元祖细胞并引导GABA能、5-羟色胺能和交感神经元分化来确认其在干性中的作用。因此，尽管没有报道GATA1在神经元谱系中的直接作用的证据，但GATA3的募集和激活对于特定神经元亚型的成熟至关重要。这篇简短的综述探讨了GATA转录因子在红细胞生成和神经元发育中的桥梁作用，强调了它们在α-突触核蛋白调节中的参与，以及它们在突触核蛋白病发病机制中的潜在作用。
