Solan: Mushrooms could provide promising leads in the search for new treatments for Alzheimer’s disease, according to a recent computational study by researchers at Jaypee University of Information Technology (JUIT), Waknaghat, Solan.
The study, titled “In silico identification of edible mushroom-derived dual cholinesterase inhibitors as potential therapeutic candidates for Alzheimer’s Disease,” was conducted by Shehriz Khan, Udayabanu M. and Tiratha Raj Singh from the Centre of Healthcare Technologies and Informatics (CEHTI), Department of Biotechnology and Bioinformatics, JUIT.
Researchers screened 21 bioactive compounds from edible and medicinal mushrooms to assess their potential to inhibit two enzymes associated with Alzheimer’s disease: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).
Among the compounds tested, ergosterol peroxide and ergosterol emerged as the strongest candidates, showing favourable predicted interactions with both enzymes.
Ergosterol peroxide shows the strongest interaction
According to the study, ergosterol peroxide, derived from Inonotus obliquus, showed the strongest predicted binding with AChE, recording a binding energy of −12.75 kcal/mol. Its predicted binding energy against BuChE was −9.66 kcal/mol.
Ergosterol, found in Agaricus bisporus, also demonstrated strong interactions, with binding energies of −11.07 kcal/mol against AChE and −8.95 kcal/mol against BuChE.
The researchers suggest that the two sterol compounds could potentially act as dual cholinesterase inhibitors, making them interesting lead molecules for further Alzheimer’s drug research.
However, the findings are based on molecular docking and do not yet demonstrate that the compounds can treat Alzheimer’s disease.
Why cholinesterase enzymes are important
Alzheimer’s disease is the most common form of dementia and accounts for approximately 60–70 per cent of dementia cases worldwide, according to the study.
The disease is associated with progressive memory impairment, cognitive decline and neuronal loss. One of the important mechanisms investigated in Alzheimer’s research is the disruption of the cholinergic system, which plays a major role in memory, learning, attention and information processing.
Acetylcholine is a key neurotransmitter in this system. As Alzheimer’s progresses, degeneration of cholinergic neurons contributes to declining acetylcholine levels.
AChE and BuChE are enzymes that break down acetylcholine. AChE is particularly important during the earlier stages of Alzheimer’s, while BuChE activity becomes more prominent as the disease advances.
The researchers therefore explored whether mushroom-derived molecules could interact with both enzymes, potentially offering a multi-target approach.
21 mushroom compounds put to the test
The JUIT team selected 21 compounds for computational screening, including ergosterol, ergosterol peroxide, pachymic acid, hispidin, antroquinonol, erinacines, ganoderic acid A, ergothioneine, cordycepin, psilocybin, hericenone B, β-glucan, gallic acid, ascorbic acid, matsutoic acid, p-coumaric acid, quercetin, caffeic acid and ferulic acid.
The molecular structures were obtained from the PubChem database and prepared for molecular docking.
The researchers used AutoDock 4.2.6 to examine how the compounds could bind to human AChE and BuChE. Protein-ligand interactions were subsequently analysed using UCSF Chimera and BIOVIA Discovery Studio.
The analysis indicated that sterol derivatives had the highest binding potential among the compounds investigated.
Triterpenoids, including pachymic acid and antroquinonol, showed moderate predicted binding, while several phenolic compounds demonstrated comparatively weaker direct interactions with the enzymes.
Mushrooms may offer more than cholinesterase inhibition
The researchers noted that a compound’s therapeutic potential cannot be judged solely by its ability to bind to AChE or BuChE.
Several mushroom-derived compounds possess antioxidant and anti-inflammatory properties, which could potentially provide neuroprotective effects through pathways other than direct cholinesterase inhibition.
For instance, compounds such as quercetin, caffeic acid, ferulic acid and gallic acid showed comparatively lower binding affinity in the study, but their known biological properties could make them relevant for further investigation.
The researchers suggest that mushroom metabolites could potentially contribute to a multi-target strategy for Alzheimer’s disease, combining cholinesterase modulation with other protective mechanisms.
Computational findings need laboratory confirmation
The study’s authors have stressed that the results are predictions generated through molecular docking and require substantial experimental validation.
Further research involving molecular dynamics simulations, enzyme-inhibition assays and in-vivo studies will be required to determine whether the compounds can actually inhibit AChE and BuChE under biological conditions.
Researchers will also need to establish their safety, stability, absorption, effectiveness and potential side effects before any consideration of therapeutic application.
The study therefore does not establish that eating mushrooms can prevent or cure Alzheimer’s disease. Instead, it identifies specific mushroom-derived molecules that could serve as starting points for future drug-development research.
Potential new direction for Alzheimer’s research
The findings place ergosterol and ergosterol peroxide among the mushroom-derived compounds that warrant further investigation as potential dual cholinesterase inhibitor candidates.
According to the researchers, their stronger predicted interactions with both AChE and BuChE support the possibility of developing sterol-based molecules capable of targeting cholinergic dysfunction at different stages of Alzheimer’s disease.
For JUIT researchers, the study provides a computational foundation for the next phase of investigation—moving from computer-based predictions to laboratory and preclinical testing.
If subsequent experiments confirm the findings, mushroom-derived sterols could potentially become useful lead compounds in the long-term search for new Alzheimer’s therapies.
