We explored the latest developments in modulators, antibody therapy, and gene therapy targeting β-site amyloid precursor protein cleaving enzyme 1 (BACE1) to combat Alzheimer's disease.
Utilizing FEL, PCA, DCCM, MM-GBSA and SIE methods, we systematically investigated the influence of phosphorylation and ligand binding on the conformational dynamics of BACE1 through Gaussian accelerated molecular dynamics (GaMD) trajectories.
Drug-like molecules designed by fragment growing strategy on isocytosine and acyl guanidine warheads as BACE1 inhibition. In vivo characterization of top-active benzimidazoles (16a, 16k) showed Aβ/oxidation stress reduction and brain/liver safety.
This review highlights the potential of multi-target-directed strategies that address amyloid-β aggregation, metal ion dyshomeostasis, and enzyme dysfunction, offering a comprehensive and effective approach to treating Alzheimer's disease.
Proaporphine alkaloids—cissamaline, cissamanine, and cissamdine—show promise against AD, with in silico studies highlighting their potential as new therapeutics.