Down regulation of DNA topoisomerase II β exerts neurodegeneration like effect through Rho GTPases in cellular model of Parkinson's disease by Down regulating tyrosine hydroxylase.

Down regulation of DNA topoisomerase IIβ exerts neurodegeneration like effect through Rho GTPases in cellular model of Parkinson's disease by Down regulating tyrosine hydroxylase. Neurol Res. 2021 Jan 05;:1-10 Authors: Yeman KB, Isik S Abstract Initiating the transcriptional activation of neuronal genes, DNA topoisomerase IIβ (topo IIβ) has a crucial role in neural differentiation and brain development. Inhibition of topo IIβ activity causes shorter axons and deteriorated neuronal connections common in neurodegenerative diseases. We previously reported that topo IIβ silencing could give rise to neurodegeneration through dysregulation of Rho GTPases and may contribute to pathogenesis of neurodegenerative diseases. Although there are several studies available proposing a link between Parkinson's Disease (PD) and Rho GTPases, there have been no reports analyzing the topo IIβ-dependent association of PD and Rho GTPases. Here, for the first time, we identified that topo IIβ has a regulatory role on Rho GTPases contributing to PD-like pathology. We analyzed the association between topo IIβ and PD by comparing topo IIβ expression levels of Retinoic Acid (RA) and Brain-derived neutrophic factor (BDNF) induced and MPP+-intoxicated SH-SY5Y cells used as an in vitro PD model. While both mRNA and protein levels of topo IIβ increase in neural differentiated cells, a significant decrease is detected in the PD model. Additionally, silenci...
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research