Journal
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 18, Issue 4, Pages -Publisher
SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2023.100835
Keywords
Extracellular vesicles; Alzheimer's disease; CB2 receptor agonist; Neurodegenerative disorders; Neuronal regeneration
Categories
Ask authors/readers for more resources
This study utilized biocompatible mesenchymal stem cell-derived extracellular vesicles (EVs) loaded with CB2 target medicine AM1241 to protect against neurodegenerative progression and neuronal function in AD model mice. The results showed that EVs-AM1241 exhibited better bioavailability and therapeutic effects than bare AM1241.
Alzheimer's disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We 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. The Morris water maze (MWM) and fear conditioning tests revealed that the leaming and memory of EVs-AM1241-treated model mice were significantly improved. In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid ,6 (A ,6 )-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated A ,6 phagocytosis, promoted neurogenesis and ultimately improved leaming and memory through the calcium-Erk signaling pathway. 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.& COPY; 2023 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available