Natural Products Targeting Amyloid Beta in Alzheimer's Disease

Int J Mol Sci. 2021 Feb 26;22(5):2341. doi: 10.3390/ijms22052341.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe brain damage and dementia. There are currently few therapeutics to treat this disease, and they can only temporarily alleviate some of the symptoms. The pathogenesis of AD is mainly preceded by accumulation of abnormal amyloid beta (Aβ) aggregates, which are toxic to neurons. Therefore, modulation of the formation of these abnormal aggregates is strongly suggested as the most effective approach to treat AD. In particular, numerous studies on natural products associated with AD, aiming to downregulate Aβ peptides and suppress the formation of abnormal Aβ aggregates, thus reducing neural cell death, are being conducted. Generation of Aβ peptides can be prevented by targeting the secretases involved in Aβ-peptide formation (secretase-dependent). Additionally, blocking the intra- and intermolecular interactions of Aβ peptides can induce conformational changes in abnormal Aβ aggregates, whereby the toxicity can be ameliorated (structure-dependent). In this review, AD-associated natural products which can reduce the accumulation of Aβ peptides via secretase- or structure-dependent pathways, and the current clinical trial states of these products are discussed.

Keywords: Alzheimer’s disease; amyloid beta; natural products; secretase-dependent; structure-dependent.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Drug Discovery
  • Humans
  • Molecular Targeted Therapy
  • Protein Aggregates / drug effects
  • Protein Conformation / drug effects
  • Signal Transduction / drug effects

Substances

  • Amyloid beta-Peptides
  • Biological Products
  • Protein Aggregates
  • Amyloid Precursor Protein Secretases