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Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aβ deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1β pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD. Schematic illustration of the synthesis and application of Glu-BSA/C1 NPs in a mouse model of Alzheimer's disease. [Display omitted] [ABSTRACT FROM AUTHOR]

The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI. Schematic illustration of the preparation and application of MG53/GMs/HA-Dex neural scaffolds in a mouse model of spinal cord injury. [Display omitted] • MGHD responded to MMP-2/9 and stably released MG53 protein with good physicochemical properties and biocompatibility. • MGHD improved the motor function of SCI mice, suppressed neuroinflammation, and promoted neurogenesis and axon regeneration. • MGHD inhibited the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]