ArticleJournal of medicinal chemistry2025
Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer's Disease.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Synthetic Heparan Sulfate-like Oligosaccharides as Tools to Decipher Growth Factor Recognition.Journal of medicinal chemistry · 2026Article
- Signaling Pathways Triggering Therapeutical Potential of Marine-Derived Polysaccharides in Alzheimer's Disease: A Recent Review.Molecular neurobiology · 2026Review
- Synthesis, Structure, and Function of Heparan Sulfate Glycopolymers to Investigate Glycosaminoglycan-Protein Interactions.Accounts of chemical research · 2026Article
- Proteoglycans are protagonists in autophagy, lymphangiogenesis, and neurodegenerative diseases.Trends in cell biology · 2026Review
- Article
- Hyperphosphorylated tau-based Alzheimer's Disease drug discovery: Identification of inhibitors of tau aggregation and cytotoxicity.SLAS discovery : advancing life sciences R & D · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
Alzheimer's disease (AD) is the most common form of dementia, marked by progressive brain degeneration and cognitive decline. A major pathological feature of AD is the accumulation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFTs), which leads to neuronal death and neurodegeneration. P-tau also induces endoplasmic reticulum (ER) stress and activates the unfolded protein response, causing inflammation and apoptosis. Additionally, p-tau spreads in the brain through interactions with heparan sulfate (HS) proteoglycans, promoting aggregation and internalization. Targeting the tau-HS interaction offers a potential therapeutic strategy for AD. We present a novel HS mimetic with a lipophilic oleanolic acid linker and a sulfated trisaccharide, which shows strong cytoprotective effects against p-tau. Moreover, this compound alleviates p-tau-induced ER stress and inflammation. Molecular docking studies indicate that the conjugation of oleanolic acid enhances binding between the ligand and tau protofilament cores, facilitating protective interactions. These findings provide a foundation for the development of novel HS mimetics, enabling further investigation of tau-HS interactions in AD and other tauopathies.
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Registered trials
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