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Intervention of the over-activated microglia-aggravated neuroinflammation represents a promising therapeutic strategy for Alzheimer's disease (AD). Upregulation of triggering receptor expressed on myeloid cells-2 (TREM2) attenuates the neuroinflammatory processes and normalizes the dysfunctional microglia. However, Trem2-gene therapy for AD by the effective non-invasive delivery systems is unexploited. Herein, we report the microglia-targeted gene delivery systems (PHSA@PF/pTREM2) composed of a core of fluorinated polyethylenimine conden