Rebalancing metal dyshomeostasis for Alzheimer's disease therapy

J Biol Inorg Chem. 2019 Dec;24(8):1159-1170. doi: 10.1007/s00775-019-01712-y. Epub 2019 Sep 5.

Abstract

Alzheimer's disease (AD) is a type of neurodegenerative malady that is associated with the accumulation of amyloid plaques. Metal ions are critical for the development and upkeep of brain activity, but metal dyshomeostasis can contribute to the development of neurodegenerative diseases, including AD. This review highlights the association between metal dyshomeostasis and AD pathology, the feasibility of rebalancing metal homeostasis as a therapeutic strategy for AD, and a survey of current drugs that action via rebalancing metal homeostasis. Finally, we discuss the challenges that should be overcome by researchers in the future to enable the practical use of metal homeostasis rebalancing agents for clinical application.

Keywords: Alzheimer’s disease; Aβ aggregation inhibitors; Metal chelators; Metal dyshomeostasis; Metal ions; Multifunctional agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism
  • Chelating Agents / therapeutic use*
  • Copper / metabolism*
  • Homeostasis / drug effects
  • Humans
  • Neuroprotective Agents / therapeutic use*
  • Protein Multimerization / drug effects
  • Zinc / metabolism*

Substances

  • Amyloid beta-Peptides
  • Chelating Agents
  • Neuroprotective Agents
  • Copper
  • Zinc