Molecular Bases of Disease
Astrocyte-specific deletion of the transcription factor Yin Yang 1 in murine substantia nigra mitigates manganese-induced dopaminergic neurotoxicity
Manganese (Mn)-induced neurotoxicity resembles Parkinson's disease (PD), but the mechanisms underpinning its effects remain unknown. Mn dysregulates astrocytic glutamate transporters, GLT-1 and GLAST, and dopaminergic function, including tyrosine hydroxylase (TH). Our previous in vitro studies have shown that Mn repressed GLAST and GLT-1 via activation of transcription factor Yin Yang 1 (YY1). Here, we investigated if in vivo astrocytic YY1 deletion mitigates Mn-induced dopaminergic neurotoxicity, attenuating Mn-induced reduction in GLAST/GLT-1 expression in murine substantia nigra (SN).Transcriptional Regulation of the Astrocytic Excitatory Amino Acid Transporter 1 (EAAT1) via NF-κB and Yin Yang 1 (YY1)
Background: The mechanism for transcriptional regulation of EAAT1 remains to be elucidated.Results: EGF-activated NF-κB is a positive regulator of EAAT1, whereas manganese-activated YY1, with HDACs acting as co-repressors, is a negative regulator.Conclusion: NF-κB and YY1 are two critical transcriptional regulators of EAAT1.Significance: Identifying the molecular targets of EAAT1 regulation is crucial to develop therapeutics against neurological disorders associated with impairment of EAAT1.
