Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer’s Disease

Abstract

An increasing number of plant-based herbal treatments, dietary supplements, medical foods and nutraceuticals and their component phytochemicals are used as alternative treatments to prevent or slow the onset and progression of Alzheimer’s disease. Their appeal stems from the fact that no current pharmaceutical or medical treatment can accomplish this. While a handful of pharmaceuticals are approved to treat Alzheimer’s, none has been shown to prevent, significantly slow or stop the disease. As a result, many see the appeal of alternative plant-based treatments as an option. Here, we show that many phytochemicals proposed or used as Alzheimer’s treatments share a common theme: they work via a calmodulin-mediated mode of action. Some phytochemicals bind to and inhibit calmodulin directly while others bind to and regulate calmodulin-binding proteins, including Aβ monomers and BACE1. Phytochemical binding to Aβ monomers can prevent the formation of Aβ oligomers. A limited number of phytochemicals are also known to stimulate calmodulin gene expression. The significance of these interactions to amyloidogenesis in Alzheimer’s disease is reviewed.

Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression

“…Interestingly, a number of natural compounds that increase ADAM10 expression are listed in Figure 3 of Manzine et al [ 71 ]. They include several phytochemicals that are proven CaM antagonists (e.g., curcumin, resveratrol, quercetin), thus offering multiple CaM-based therapeutic agents for further study [ 72 ].…”

“…Identifying critical CaMBPs involved in AD could provide more precise therapeutic targets than those directed at calcium. Many approved pharmaceuticals and phytochemicals exist that target CaM and specific CaMBPs that could be employed quickly as AD therapeutics [ 23 , 72 ].…”

Antihyperlipidemic activity of myricetin

“…It may be accompanied by severe myolysis side effects and certain neurotoxicity, among which muscle pain caused by myolysis side effects is only triggered by statins. However, plants usually contain phytochemicals with various physiological activities, including some compounds with high activity and almost non-toxic side effects, such as some flavonoids, and appropriate supplementation helps prevent various diseases (O'Day, 2023).…”