Alzheimer's disease is a
neurodegenerative disease that was conventionally thought to be related to the sedimentation of beta-amyloids, but drugs designed according to this hypothesis have generally failed. That
FKBP52 can reduce the accumulation of
tau proteins, and that
Tacrolimus can reduce the pathological changes of
tau proteins are new directions away from the long held
amyloid-beta-centric concept. Therefore, the screening of
traditional Chinese medicine compounds for those with higher affinity towards
FKBP52 than
Tacrolimus may be a new direction for treating
Alzheimer's disease. This study utilizes
ligand-based and structure-based methods as the foundation. By utilizing dock scores and the predicted pIC50 from SVM, MLR, and Bayesian Network, several TCM compounds were selected for further analysis of their
protein-
ligand interactions.
Daphnetoxin has higher affinity and complex structure stability than
Tacrolimus; Lythrancine II exhibits the most identical trends in
FKBP52 interactions as
Tacrolimus, and 20-O-(2'E,4'E-decadienoyl)ingenol may be further modified at its
hydrocarbon chain to promote interaction with
FKBP52. In addition, we observed the residue Tyr113 of
FKBP52 may play a key role in
protein-
ligand interaction. Our results indicate that
Daphnetoxin, 20-O-(2'E,4'E-decadienoyl)ingenol, and Lythrancine II may be starting points for further modification as a new type of non-
amyloid-beta-centric
drug for
Alzheimer's disease.