The extracellular matrix enriched with membrane metalloendopeptidase and insulin-degrading enzyme suppresses the deposition of amyloid-beta peptide in Alzheimer's disease cell models

摘要

Amyloid plaque is a typical feature of Alzheimer's disease (AD) and is one of the targets for AD therapy. Membrane metalloendopeptidase (MME) and insulin-degrading enzyme (IDE) are two types of proteases that could cleave beta-amyloid (A beta) peptides generated by neuron cells of AD patients. Extracellular matrix (ECM) plays a crucial role in regulating tissue-specific functions and is an ideal biomaterial for tissue repair. In this study, we extracted the liquid ECM enriched with collagen-binding-domain-fused IDE or MME from human foreskin fibroblast cells. We found that these ECM biomaterials reduced the aggregation of A beta peptides, prevented the formation of amyloid plaques, and also suppressed phosphorylation of Tau protein in AD cell models. Overall, our research provides a novel ECM biomaterial that can be potentially used for AD therapy.