Microglial SIX2 suppresses lipopolysaccharide (LPS)-induced neuroinflammation by up-regulating FXYD2 expression.

Parkinson's disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation.

Dephosphorylation of Six2Y129 protects tyrosine hydroxylase-positive cells in SNpc by regulating TEA domain 1 expression.

Parkinson's disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We recently reported that Six2 could reverse the degeneration of DA neurons in a dephosphorylation state. Here we further identified that Eya1 was the phosphatase of Six2 that could dephosphorylate the tyrosine 129 (Y129) site by forming a complex with Six2 in damaged DA cells.

Smarcd1 antagonizes the apoptosis of injured MES23.5 DA cells by enhancing the effect of Six2 on GDNF expression.

Glial cell line-derived neurotrophic factor (GDNF) played critical roles in the survival and repair of dopaminergic (DA) neurons. Transcription factor Six2 could repair injured DA cells by promoting the expression of GDNF, however, the underlying molecular mechanisms remain largely unknown. In this study, we screened forty-three proteins that interacted with Six2 in MES23.