Component of Cannabis, Cannabidiol, as a Possible Drug against the Cytotoxicity of Abeta(31-35) and Abeta(25-35) Peptides: An Investigation by Molecular Dynamics and Well-Tempered Metadynamics Simulations
In this work cannabidiol (CBD) was investigated as a possible drug against the cytotoxicity of Aβ(31-35) and Aβ(25-35) peptides with the help of atomistic molecular dynamics (MD) and well-tempered metadynamics simulations. Four interrelated mechanisms of possible actions of CBD are proposed from our computations. This implies that one mechanism can be a cause or/and a consequence of another. CBD is able to decrease the aggregation of peptides at certain concentrations of compounds in water. This particular action is more prominent for Aβ(25-35), since originally Aβ(31-35) did not exhibit aggregation properties in aqueous solutions. Interactions of CBD with the peptides affect secondary structures of the latter ones. Clusters of CBD are seen as possible adsorbents of Aβ(31-35) and Aβ(25-35) since peptides are tending to aggregate around them. And last but not least, CBD exhibits binding to MET35. All four mechanisms of actions can possibly inhibit the Aβ-cytotoxicity as discussed in this paper. Moreover, the amount of water also played a role in peptide clustering: with a growing concentration of peptides in water without a drug, the aggregation of both Aβ(31-35) and Aβ(25-35) increased. The number of hydrogen bonds between peptides and water was significantly higher for simulations with Aβ(25-35) at the higher concentration of peptides, while for Aβ(31-35) that difference was rather insignificant. The presence of CBD did not substantially affect the number of hydrogen bonds in the simulated systems.
Keywords: Alzheimer’s disease; Cannabis; cannabidiol; metadynamics; molecular dynamics.
Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).
Phys Biol. 2013 Aug;10(4):040301. doi: 10.1088/1478-3975/10/4/040301. Epub 2013 Aug 2. Phys Biol. 2013. PMID: 23912807
Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement.
Phytother Res. 2014 Jul;28(7):1007-13. doi: 10.1002/ptr.5095. Epub 2013 Nov 28. Phytother Res. 2014. PMID: 24288245
Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer’s disease.
Eur J Med Chem. 2020 Apr 15;192:112163. doi: 10.1016/j.ejmech.2020.112163. Epub 2020 Feb 22. Eur J Med Chem. 2020. PMID: 32109623 Review.
Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression.
Br J Pharmacol. 2007 Aug;151(8):1272-9. doi: 10.1038/sj.bjp.0707337. Epub 2007 Jun 25. Br J Pharmacol. 2007. PMID: 17592514 Free PMC article.
Effects of cannabidiol (CBD) in neuropsychiatric disorders: A review of pre-clinical and clinical findings.
Prog Mol Biol Transl Sci. 2019;167:25-75. doi: 10.1016/bs.pmbts.2019.06.005. Epub 2019 Aug 28. Prog Mol Biol Transl Sci. 2019. PMID: 31601406 Review.