Targeted nanoplatform reduces microglial senescence and eases motor deficits in Parkinson mice

In human substantia nigra single-cell data and mouse models of Parkinson's disease, researchers investigated how targeting the PLXDC2 gene affects disease progression. By analyzing the human tissue atlas, the team identified elevated PLXDC2 expression in microglia. They then engineered a biomimetic nanoplatform coated with a ferritin-modified microglial membrane to deliver PLXDC2-silencing siRNA alongside the iron chelator deferoxamine and antioxidant cerium oxide nanoparticles. In mice with Parkinson's disease, the nanoplatform successfully crossed the blood-brain barrier. The intervention decreased iron deposition, diminished reactive oxygen species, and curbed neuroinflammation. Silencing PLXDC2 mitigated microglial senescence driven by the cGAS-STING signaling pathway. Consequently, the treated mice experienced reduced dopaminergic neurodegeneration and showed measurable improvements in motor performance, including balance, coordination, and endurance.