Constructing Curcumin-Based Biological Metal-Organic Frameworks (MOFs) for the Treatment of Alzheimer's Disease Through the Pyroptosis Pathway.

Abstract

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder that presents as neuronal cell death caused by the pyroptosis pathway. Currently, curcumin is widely reported in the treatment of AD due to its dual inhibitory effects on NLRP3-associated inflammasome activation, but it suffers from poor bioavailability. Therefore, in this study, a highly stable curcumin-based Zn-organic framework (medi-MOF-1) loaded with taxifolin (TAX@medi-MOF-1) was presented to overcome the defect with a specific surface area of 2530.652 mg. The loaded TAX could further enhance the anti-inflammatory and antioxidant properties. In 5×FAD transgenic mice, TAX@medi-MOF-1 significantly improved cognitive and motor functions, reduced Aβ plaque deposition, and downregulated key pyroptosis proteins (NLRP3, caspase-1, and GSDMD-N). The dual-drug system exhibited synergistic effects, offering a promising multi-target therapeutic strategy for AD.