Neurotoxicity of metal mixtures

Vanda Lopes de Andrade, Ana Paula Marreilha dos Santos, Michael Aschner

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Environmental exposures and/or alterations in the homeostasis of essential transition metals (ETM), such as Fe, Cu, Zn or Mn, are known to contribute to neurodegenerative diseases (ND), such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). Aberrant ETM homeostasis leads to altered distributions, as significant amounts may accumulate in specific brain areas, while causing metal deficiency in others. The disruption of processes reliant on the interplay between these ETM, may lead to loss of metal balance and the ensuing neurotoxicity via shared mechanisms, such as the induction of oxidative stress (OS). Both ETM imbalance and OS may play a role, via complex positive loop processes, in primary neuropathological signatures of AD, such as the accumulation of amyloid plaques and neurofibrillary tangles (NTF), and in PD, α-Syn aggregation and loss of dopamine(DA)rgic neurons. The association between ETM imbalance and ND is rarely approached under the view that metals such as Fe, Cu, Zn and Mn, can act as dangerous endogenous neurotoxic mixtures when their control mechanisms became disrupted. In fact, their presence as mixtures implies intricacies, which should be kept in mind when developing therapies for complex disorders of metal dyshomeostasis, which commonly occur in ND.

Original languageEnglish (US)
Title of host publicationNeurotoxicity of Metals
Subtitle of host publicationOld Issues and New Developments
EditorsMichael Aschner, Lucio G. Costa, Lucio G. Costa
PublisherElsevier Inc.
Pages329-364
Number of pages36
ISBN (Print)9780128237755
DOIs
StatePublished - Jan 2021

Publication series

NameAdvances in Neurotoxicology
Volume5
ISSN (Electronic)2468-7480

Keywords

  • Alzheimer disease
  • Amyloid plaques
  • Dopamine oxidation
  • Essential transition metals mixtures
  • Fe-Cu-Zn-Mn dyshomeostasis
  • Levy Bodies
  • Neurofibrillary tangles
  • Oxidative stress
  • Parkinson disease

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Health, Toxicology and Mutagenesis

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