Blocking Memory Loss: Delta Opioid Receptor Antagonists Prevent Alzheimer’s Pathology
- Zhandos Sembay
- Sep 25
- 2 min read
New Class of Compounds Shows Neuroprotection, Plaque Reduction, and Strong Drug-Like Properties
Birmingham, AL – Sep 25, 2025 – Alzheimer’s disease, a devastating neurodegenerative condition affecting over 55 million people worldwide, has long lacked effective preventative treatments. Now, a collaborative team including SPARC representative Dr. Sixue Zhang has helped lead the development of a new class of delta opioid receptor (DOR) antagonists that prevent Alzheimer’s-like pathology in preclinical models. The study, published in ACS Pharmacology & Translational Science (IF = 5.0), represents a major step toward a preventative therapy for dementia.
🧾 Read the article here: https://pubs.acs.org/doi/10.1021/acsptsci.5c00509
Discovery Highlights
Through medicinal chemistry and pharmacological innovation, the research team identified and validated compounds that block delta opioid receptor activity. Key outcomes include:
Novel DOR antagonists synthesized with strong brain penetration and favorable pharmacokinetics
Prevention of hallmark Alzheimer’s pathology, including amyloid plaque buildup and tau-related changes
Neuroprotective effects, preserving neuronal health in preclinical models
Drug-like properties supportive of advancing to human clinical studies
Impact & Next Steps
This collaborative effort underscores the importance of receptor biology in dementia research, with SPARC’s contribution at the forefront:
🧠 SPARC scientist Dr. Sixue Zhang played a critical role in the discovery pipeline, ensuring rigorous pharmacological testing and translational focus.💥 The compounds represent a first-in-class approach, preventing Alzheimer’s-like damage before symptoms emerge.🧬 With strong drug-like properties and neuroprotective action, these antagonists are primed for future clinical development.
Behind the Scenes
This research was made possible through a multidisciplinary collaboration between SPARC, University of Alabama at Birmingham, and partner institutions. The author team brings together expertise spanning pharmacology, neuroscience, and medicinal chemistry.
References
Tanguturi P, Mitchell S, Moukha-Chafiq O, Zhang S, Tillotson J, Ananthan S, Augelli-Szafran CE, Streicher JM. Development of Delta Opioid Receptor Antagonists Which Prevent Alzheimer's Disease-Like Pathology in the 5X-Familial Alzheimer's Disease [5XFAD] Mouse Model. ACS Pharmacology & Translational Science. 2025 Aug 5;8(9):3346-3370. doi:10.1021/acsptsci.5c00509. PMID: 40969869; PMCID: PMC12441865.
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