Exploring Multitarget Strategies for Membrane Protection in Alzheimer's Disease

ACS Chem Neurosci. 2023 Nov 15;14(22):3972-3974. doi: 10.1021/acschemneuro.3c00627. Epub 2023 Oct 24.

Abstract

The exploration of multitarget molecules presents a promising avenue in the quest for effective therapeutic strategies against Alzheimer's disease (AD), a multifactorial neurodegenerative disorder. Traditional single-target drugs have shown limited success due to the complex interplay of pathological processes involved in AD. Multitarget-directed ligands (MTDLs), designed to interact with multiple targets simultaneously, offer a more holistic approach to address the multifaceted nature of neurodegenerative diseases. Recent studies have highlighted the potential of chalcones and huprine derivatives in mitigating amyloid-β peptide-associated toxicity and preserving membrane integrity, crucial for cellular homeostasis. The interaction of these compounds with lipid bilayers may modulate biological responses, opening a new realm of investigation in membrane-centric phenomena. This approach not only broadens the mechanistic understanding of bioactive compounds but also underscores the need for a paradigm shift in AD research, focusing on both intracellular targets and plasma membrane protection for more effective treatment strategies.

Keywords: Alzheimer’s disease; chalcones; huprine derivatives; lipid bilayer; multitarget molecules; plasma membrane.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Cholinesterase Inhibitors / therapeutic use
  • Humans
  • Ligands

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Ligands