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Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer’s Disease
Sanyong Zhu, Zhenfeng Song, April Sweet Tapayan, Kartikey Singh, Kuang‐Wei Wang, Hsiao‐Tien Chien Hagar, Jicheng Zhang, Hyunbae Kim et al.. Journal of Medicinal Chemistry, 2025-01-22
Topic: Brain proteins, microglia and lab models
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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhu, S., Song, Z., Tapayan, A. S., Singh, K., Wang, K., Hagar, H. C., et al. (2025). Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer’s Disease. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.4c02563
Vancouver
Zhu S, Song Z, Tapayan AS, Singh K, Wang K, Hagar HC, et al. Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer’s Disease. Journal of Medicinal Chemistry. 2025. doi:10.1021/acs.jmedchem.4c02563. PMID: 39842821.
BibTeX
@article{zhu2025-39842821,
author = {Zhu, Sanyong and Song, Zhenfeng and Tapayan, April Sweet and Singh, Kartikey and Wang, Kuang‐Wei and Hagar, Hsiao‐Tien Chien and Zhang, Jicheng and Kim, Hyunbae and others},
title = {{Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer’s Disease}},
journal = {Journal of Medicinal Chemistry},
year = {2025},
doi = {10.1021/acs.jmedchem.4c02563},
pmid = {39842821},
url = {https://doi.org/10.1021/acs.jmedchem.4c02563}
}
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Key findings
- 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.
Why it matters
A newly made heparan sulfate mimetic compound protected cells against hyperphosphorylated tau and reduced tau-induced ER stress and inflammation in laboratory experiments. This is early, cell-based work, and the authors present it only as a foundation for further investigation of tau-heparan sulfate interactions.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Medicinal Chemistry) |
| Journal's citation record | 3 / 4 | Journal of Medicinal Chemistry: journal h-index 373 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 10 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hien M. Nguyen: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Michigan State University: institution h-index 1,089 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39842821) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1021/acs.jmedchem.4c02563
- PubMed: 39842821
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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