Copper, iron, selenium and lipo-glycemic dysmetabolism in alzheimer’s disease

Jan Aaseth, Anatoly V. Skalny, Per M. Roos, Jan Alexander, Michael Aschner, Alexey A. Tinkov

Research output: Contribution to journalReview articlepeer-review

Abstract

The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer’s disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroin-flammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenu-ate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.

Original languageEnglish (US)
Article number9461
JournalInternational Journal of Molecular Sciences
Volume22
Issue number17
DOIs
StatePublished - Sep 1 2021

Keywords

  • Advanced glycation end-products
  • Copper
  • GLP-1 agonist
  • Glycemic dysregulation
  • Iron
  • Selenium

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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