GATA Transcription Factors: A Cross-Road for Erythropoiesis, Neurodevelopment, and Synucleinopathies

Abstract

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.