Forest Organism Holds Secret to Slowing Alzheimer’s Damage

Bringing attention to one of the most challenging brain diseases today, Alzheimer’s continues to affect millions of people worldwide with memory loss, confusion, and steady mental decline. What makes this disease especially harmful is the buildup of harmful proteins in the brain, called amyloid-beta (Aβ), which group together and damage nerve cells. Although there are medicines that help manage some symptoms, none can fully stop the disease from getting worse. Because of this, scientists are searching for new ways to treat Alzheimer’s, and one promising path involves natural substances found in plants and fungi.

Lichen, a symbiotic organism formed from fungi and algae, serve as terrestrial pioneer species and environmental indicators in colonizating terrestrial environments. They play essential ecological roles, particularly in extreme high-altitude regions, such as the Qinghai–Tibetan Plateau (Himalayan Plateau) and other alpine zones worldwide. To survive harsh conditions, lichen have evolved robust secondary metabolic pathways, generating a diverse array of structurally unique and stable chemical compounds. These natural products represent a vast and underexplored reservoir for drug discovery.

Coming from a team at The Hong Kong University of Science and Technology (HKUST), led by Dr. Meixia Yang and Professor Karl Tsim, has uncovered a promising Alzheimer’s-related finding. Their study demonstrates that gyrophoric acid—a natural compound derived from lichen—can both inhibit the formation of harmful protein clumps (Aβ  aggregates) in the brain and disaggregate existing ones. This work has been published in the International Journal of Molecular Sciences. 

Combining computer simulations with real lab tests, the researchers showed how gyrophoric acid works. The compound sticks to specific parts of the harmful Aβ  aggregates and prevents it from changing into the sticky form that builds up in Alzheimer’s. Instead of using strong bonds like some drugs do, gyrophoric acid uses gentler connections—mainly based on hydrophobic forces, which are interactions where water-repelling regions of molecules come together—to hold the protein in a harmless form. In lab tests, gyrophoric acid started breaking down these Aβ  aggregates  within a few hours, and by the end of the day, most of the large aggregates were gone.

Professor Tsim explained, “Our study demonstrates that gyrophoric acid interacts with key hydrophobic residues of Aβ through a conformational selection mechanism.” These hydrophobic residues are the water-repelling parts of the protein. The conformational selection mechanism means that the compound works by locking the protein into a safe shape before it turns harmful. “This allows it to disrupt both early and late-stage fibril formation.” Fibrils are the harmful, thread-like structures that form when the protein clumps together. Using a dye that glows in the presence of these protein clumps, along with powerful confocal microscopes—special tools that allow researchers to see fine details inside cells—the team watched the treatment work in real time.

Fascinatingly, gyrophoric acid doesn’t just stop Aβ from clumping—it also breaks apart the clumps that have already formed. This is a rare and helpful trait, especially since many Alzheimer’s treatments struggle to deal with these older, sticky protein forms. Because the compound connects in a softer and more targeted way, it might also cause fewer unwanted effects compared to stronger drugs that can stick to the wrong places in the body.

Exploring its safety and usefulness, the team also looked at how the body might absorb and handle gyrophoric acid. They found it follows several key rules for drug-likeness, a term that means how well a compound might work as a medicine inside the human body. One such rule is Lipinski’s rule of five, a guideline used in drug development to predict if a compound can be absorbed when taken by mouth. While gyrophoric acid might not easily cross into the brain due to its molecular structure, its ability to strongly hold onto its target protein could help balance that out. “Gyrophoric acid demonstrates a rare combination of strong binding, metabolic stability, and low cytotoxicity,” said Dr. Yang. Metabolic stability refers to how long a substance remains active in the body without being broken down, and low cytotoxicity means it is not harmful to healthy cells.

Looking at the bigger picture, this research brings attention to lichens that survive in tough environments by producing unique and stable chemicals. Gyrophoric acid is one of these natural substances, and the scientists believe other similar compounds in lichens could be just as helpful. Searching through different lichens could uncover even more natural chemicals that might help fight Alzheimer’s.

Shifting focus to future possibilities, the researchers say more tests are needed in living systems, known as in vivo testing, to see how well gyrophoric acid works and how it can be delivered effectively to the brain. “The natural chemodiversity found in lichens remains largely untapped,” said Dr. Yang. Chemodiversity refers to the variety of chemical structures found in nature. “We believe this is only the beginning. Derivatives of gyrophoric acid or similar structures may be optimized further for clinical use.”

Working against a disease expected to become much more common in the coming decades, this study highlights a promising new option. Gyrophoric acid not only stops the formation of harmful protein buildup in the brain, but also clears away what’s already there. Paired with its safety and potential for future development, it offers hope in the ongoing effort to find better solutions for treating Alzheimer’s.

Journal Reference

Yang M., Hu H., Gao J., Lai Q.W.S., Eshboev F., Leung K.W., Dong T.T., Xu Q., Tsim K.W.K. “The Identification of Gyrophoric Acid, a Phytochemical Derived from Lichen, as a Potent Inhibitor for Aggregation of Amyloid Beta Peptide: In Silico and Biochemical Evaluation.” International Journal of Molecular Sciences, 2025; 26(17): 8500. DOI: https://doi.org/10.3390/ijms26178500

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