Potential Retinoid X Receptor Agonists for Treating Alzheimer’s Disease from Traditional Chinese Medicine

Abstract

Alzheimer's disease is neurodegenerative disorder due to the accumulation of amyloid-β in the brain and causes dementia with ageing. Some researches indicate that the RXR agonist, Targretin, has also been used for treatment of Alzheimer's disease in mouse models. We investigate the potent candidates as RXR agonists from the vast repertoire of TCM compounds in TCM Database@Taiwan. The potential TCM compounds, β-lipoic acid and sulfanilic acid, had higher potent binding affinities than both 9-cis-retinoic acid and Targretin in docking simulation and have stable H-bonds with residues Arg316 and some equivalent hydrophobic contacts with residues Ala272, Gln275, Leu309, Phe313, Val342, Ile345, and Cys432 as Targretin. The carboxyl or sulfonyl hydroxide group can form a H-bond with key residue Arg316 in the docking pose, and the phenyl group next to the carboxyl or sulfonyl hydroxide group can form a π interaction with residue Phe313. Moreover, β-lipoic acid and sulfanilic acid have stable H-bonds with residue Gln275, Ser313, and residue Ala327, respectively, which may strengthen and stabilize TCM candidates inside the binding domain of RXR protein. Hence, we propose β-lipoic acid and sulfanilic acid as potential lead compounds for further study in drug development process with the RXR protein against Alzheimer's disease.

Alzheimer Disease: Clues from traditional and complementary medicine

“…Forming viable bonds with the RXR protein receptors, these TCM compounds exhibit potential to be developed into anti-dementia drugs. 25 …”

Computational Study of Asian Propolis Compounds as Potential Anti-Type 2 Diabetes Mellitus Agents by Using Inverse Virtual Screening with the DIA-DB Web Server, Tanimoto Similarity Analysis, and Molecular Dynamic Simulation

“…These proteins facilitate gene transcription by regulating lipids, insulin sensitivity, and glucose homeostasis. The proteins mentioned earlier are used as diabetes targets to treat T2DM [136]. PPAR protein isomer (PPARA, PPARD, PPARG) activity is interconnected to regulate other protein targets in different categories, such as GCK and HSD11B1 by PPARG and PDK2 by PPARD and PPARA [18].…”