Author(s)

Yang Li^1,2, Fengyuan Zhang^1,3, Caroline E. Herron^1,4, Ivonne Rosales⁵, Alejandro Heredia⁶, Nicolae-Viorel Buchete^3,7, Brian J. Rodriguez^1,3

¹Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
²Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
³School of Physics, University College Dublin, Dublin, Ireland.
⁴School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
⁵Departamento de Física y Química Teórica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico.
⁶Laboratorio de Evolución Química, Departamento de Química de Radiaciones y Radioquímica, Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Mexico City, Mexico.
⁷Institute for Discovery, University College Dublin, Dublin, Ireland.

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.

Cannabidiol, Amyloid, Alzheimer’s Amyloid-β Peptides, Aβ-Derived Diffusible Ligands, Atomic Force Microscopy, Amyloid Peptide Sequestration

Li, Y. , Zhang, F. , Herron, C. , Rosales, I. , Heredia, A. , Buchete, N. and Rodriguez, B. (2023) Cannabidiol-Mediated Sequestration of Alzheimer’s Amyloid-β Peptides in ADDL Oligomers. American Journal of Molecular Biology, 13, 113-126. doi: 10.4236/ajmb.2023.132008.