In Silico Screening of Hericium Genus Metabolites Against Beta-Secretase: A Therapeutic Insight into Alzheimer’s Disease.

Computer-aided drug design (CADD) quickens the progress of new therapies by using in silico modelling to identify potential neuroprotective agents. Studying erinacines S, A, and C as potential Alzheimer's disease (AD) treatments, we explore the potential of natural bioactive compounds from the mushroom genus Hericium. Erinacine S appears to lessen the buildup of amyloid-beta (Aβ) plaques by boosting nerve growth factor (NGF) levels and crossing the blood-brain barrier. Erinacine C helps regulate glial-derived neurotrophins and displays anti-inflammatory effects in the brain, while erinacine A activates neurotrophic signalling pathways and promotes the growth of new neurons in the hippocampus. In addition, we examine novel compounds that may help counteract endoplasmic reticulum (ER) stress and restore estrogen receptor function—both of which are disrupted in AD. In particular, the dysfunction of estrogen receptor alpha (erα) and the increased activity of beta-secretase (BACE1) are highlighted as key contributors to disease progression. Through molecular docking studies, we evaluate how Hericium-derived compounds interact with BACE1, suggesting a promising natural product-based approach to developing new therapies for Alzheimer’s disease.