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

CNS Neurosci Ther. 2018 Sep;24(9):753-762. doi: 10.1111/cns.12971. Epub 2018 May 16.

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.

Keywords: Alzheimer’s disease; cholinesterase; curcumin; gallocatechins; polyphenols; resveratrol.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Cholinesterase Inhibitors / administration & dosage*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterases / metabolism
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends*
  • Humans
  • Polyphenols / administration & dosage*
  • Polyphenols / chemistry
  • Polyphenols / metabolism
  • Treatment Outcome
  • tau Proteins / antagonists & inhibitors
  • tau Proteins / metabolism

Substances

  • Cholinesterase Inhibitors
  • Polyphenols
  • tau Proteins
  • Cholinesterases