TITLE:
Cannabidiol-Mediated Sequestration of Alzheimer’s Amyloid-β Peptides in ADDL Oligomers
AUTHORS:
Yang Li, Fengyuan Zhang, Caroline E. Herron, Ivonne Rosales, Alejandro Heredia, Nicolae-Viorel Buchete, Brian J. Rodriguez
KEYWORDS:
Cannabidiol, Amyloid, Alzheimer’s Amyloid-β Peptides, Aβ-Derived Diffusible Ligands, Atomic Force Microscopy, Amyloid Peptide Sequestration
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.13 No.2,
March
3,
2023
ABSTRACT: Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits processes relating to amyloid beta (Aβ)-induced neurotoxicity in mouse models of Alzheimer’s disease, though the detailed molecular mechanism underlying the CBD neurotoxicity modulation is not fully understood. In this study, using atomic force microscopy, we find that CBD promotes the aggregation of Aβ peptides, enhancing the formation of Aβ oligomers, also known as Aβ-derived diffusible ligands (ADDLs). The CBD-mediated sequestration of Aβ monomers in soluble ADDLs could reduce neurotoxicity. This study highlights a possible role of CBD in modulating the formation of ADDL aggregates and provides insight into potentially neuroprotective properties of CBD in Alzheimer’s disease.