Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of β-amyloid (Aβ) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances. Approximately, 60%-80% of all cases of dementia in the world are patients with AD. In view of the continuous rise of this disease especially in the aged population, there is a dire need to come up with a novel compound and/or mixture that could work against this devastating disease. In this regard, the best is to rely on natural compounds rather than synthetic ones, because natural compounds are easily available, cost-effective, and comparatively less toxic. To serve this purpose, lately, scientific community has started exploring the possibility of using different polyphenols either solitary or in combination that can serve as therapeutics against AD. In the current article, we have summarized the role of various polyphenols, namely quercetin, resveratrol, curcumin, gallocatechins, cinnamic acid, caffeine, and caffeic acid as an inhibitor of cholinesterase for the treatment of AD. We have also tried to uncover the mechanistic insight on the action of these polyphenols against AD pathogenicity.

Activity-guided purification reveals quercetin as the most efficient cholinesterase inhibitor in wild strawberry (Fragaria vesca L.) and apricot (Prunus armeniaca L.) fruit extract

“…In particular, Orhan et al (2007) pointed out quercetin as a substantially more efficient AChE inhibitor than a number of well-known polyphenolic compounds (luteolin-7-O-rutinoside, chlorogenic acid, caffeic acid, gallic acid, apigenin, genistein, kaempferolgalactoside, naringin, diosmin, silibinin, silymarin). The above-mentioned facts have been widely confirmed by other authors recently (Jabir et al, 2018;Khaw et al, 2018). Fig 7. 1 H-NMR spectrum of compound 1 (peak 1 with RT 54 min.…”

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

“…The malfunction of meningeal lymphatic vessel (the other cleaner of Aβ deposits closely related to lymphatic system) was found to be greatly associated with AD pathogenesis . In the meantime, some immunotherapies and drugs for Aβ clearance have attempted to control progress of AD . For example, a monoclonal antibody‐based immunotherapeutic drug was reported under development in recent year, and it selectively targeted and cleared the aggregated Aβ in brain and effectively relieved the symptom of AD …”

Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

“…It is widely accepted that neurodegenerative diseases are associated with chronic CNS inflammation . As an efficient inflammation amplifier, inflammasome activation could be the result of neurodegeneration as well as the reason for the disease progression.…”

“…It is widely accepted that neurodegenerative diseases are associated with chronic CNS inflammation. 29,30 As an efficient inflam-…”