Cannabidiol-Mediated Sequestration of Alzheimer’s Amyloid-β Peptides in ADDL Oligomers  

作　　者：Yang Li Fengyuan Zhang Caroline E. Herron Ivonne Rosales Alejandro Heredia Nicolae-Viorel Buchete Brian J. Rodriguez Yang Li;Fengyuan Zhang;Caroline E. Herron;Ivonne Rosales;Alejandro Heredia;Nicolae-Viorel Buchete;Brian J. Rodriguez(Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland;Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China;School of Physics, University College Dublin, Dublin, Ireland;School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland;Departamento de Física y Química Teórica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico;Laboratorio de Evolución Química, Departamento de Química de Radiaciones y Radioquímica, Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Mexico City, Mexico;Institute for Discovery, University College Dublin, Dublin, Ireland)

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

出　　处：《American Journal of Molecular Biology》2023年第2期113-126,共14页美国分子生物学期刊（英文）

摘　　要：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 (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.

关 键 词：CANNABIDIOL AMYLOID Alzheimer’s Amyloid-β Peptides Aβ-Derived Diffusible Ligands Atomic Force Microscopy Amyloid Peptide Sequestration 

分 类 号：R74[医药卫生—神经病学与精神病学]