Lnc-USP28-6/ZBTB16 axis orchestrates NLRP3 inflammasome activation and α-synuclein SUMOylation to drive Parkinson's disease pathogenesis - PubMed
8 hours ago
- #Parkinson's disease
- #Neuroinflammation
- #SUMOylation
- The study explores the role of the lnc-USP28-6/ZBTB16 axis in Parkinson's disease (PD) pathogenesis.
- ZBTB16 is upregulated in PD patients' peripheral blood mononuclear cells (PBMCs) and postmortem striatal tissues.
- ZBTB16 overexpression enhances α-synuclein (α-syn) expression and aggregation via transcriptional activation and post-translational modifications.
- ZBTB16-dependent UBC9 upregulation increases SUMO1+/α-syn+ cells, with knockdown reversing this effect.
- ZBTB16 amplifies NLRP3 inflammasome activation, Gasdermin D (GSDMD) expression, and IL-1β/IL-18 secretion in microglial models.
- lnc-USP28-6 transcriptionally upregulates ZBTB16 and α-syn in SH-SY5Y cells, independent of rotenone (ROT) exposure.
- The lnc-USP28-6/ZBTB16 axis drives PD through neuroinflammation and α-syn aggregation, suggesting potential therapeutic targets.