EVs-mediated delivery of CB2 receptor agonist for Alzheimer’s disease therapy

Asian Journal of Pharmaceutical Sciences, 2023 · DOI: https://doi.org/10.1016/j.ajps.2023.100835 · Published: August 4, 2023

Pharmacology Neurology

Simple Explanation

Alzheimer's disease (AD) leads to irreversible neuronal degeneration, and effective treatment remains elusive. This study uses mesenchymal stem cell-derived extracellular vesicles (EVs) loaded with AM1241 to protect against neurodegenerative progression in AD model mice. The EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. Tests showed learning and memory of EVs-AM1241- treated model mice were significantly improved. EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice. EVs-AM1241 are very promising particles for treating AD.

Study Duration

2 weeks

Participants

APP/PS1 mice and WT littermates

Evidence Level

Not specified

Key Findings

1
EVs-AM1241 increased the amount of AM1241 in the brain and improved the biocompatibility of AM1241.
2
EVs-AM1241 significantly improved the response of neurons in the hippocampal CA1 region to stimuli, improving neuronal function.
3
EVs-AM1241 facilitated A β phagocytosis, promoted neurogenesis and improved learning and memory through the calcium-Erk signaling pathway.

Research Summary

The study utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.

Practical Implications

Enhanced Drug Delivery

EVs can be used to deliver drugs across the blood-brain barrier, improving drug concentration in the brain.

Improved Biocompatibility

EVs can improve the biocompatibility of drugs, reducing side effects.

Therapeutic Target

CB2R may act as a therapeutic target for AM1241-loaded EVs.

Study Limitations

1
The side effects of long-term treatment with EVs need to be considered when developing therapeutic strategies for NDs.
2
The mechanisms by which EVs function remain unclear.
3
Not specified

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