Postdoc/Ph.D. Kaohsiung Medical University Kaohsiung Medical University, Kaohsiung, Taiwan
Abstract: Jun dimerization protein 2 (Jdp2) gene is expressed in mouse cerebellar granule cell progenitors (GCPs), where its encoded protein plays a pivotal role in cerebellum lobule formation through programmed cell death. However, the precise role of Jdp2 in cellular differentiation, pluripotency, and its interaction with antioxidative mechanisms in the cerebellum remains poorly understood. In the present study, we investigate the impact of N-acetyl-L-cysteine (NAC) on the early commitment of granule cell precursors (GCPs) to neuronal fates, particularly Purkinje cells, through the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis. We find that Jdp2-depletion enhances the differentiation of GCPs towards Purkinje cells in vitro. The antioxidative action of NAC drives this differentiation process, particularly in the presence of Gabra6, suggesting that NAC can potentiate the transdifferentiating of GCPs into Purkinje cells. These findings highlight the potential of antioxidative treatments as therapeutic strategies for rescuing oxidative stress-induced damage in GCPs and guiding their differentiation into Purkinje cells.
Refs. Sci Rep. 2020 Mar 18;10(1):4933; Stem Cell Res Ther. 2021 Jun 29;12(1):369; Cell Death Discov. 2024 Dec 18;10(1):500.