The aging brain: impact of heavy metal neurotoxicity

Crit Rev Toxicol. 2020 Oct;50(9):801-814. doi: 10.1080/10408444.2020.1838441. Epub 2020 Nov 19.


The aging process is accompanied by critical changes in cellular and molecular functions, which upset the homeostatic balance in the central nervous system. Accumulation of metals renders the brain susceptible to neurotoxic insults by mechanisms such as mitochondrial dysfunction, neuronal calcium-ion dyshomeostasis, buildup of damaged molecules, compromised DNA repair, reduction in neurogenesis, and impaired energy metabolism. These hallmarks have been identified to be responsible for neuronal injuries, resulting in several neurological disorders. Various studies have shown solid associations between metal accumulation, abnormal protein expressions, and pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and Amyotrophic lateral sclerosis. This review highlights metals (such as manganese, zinc, iron, copper, and nickel) for their accumulation, and consequences in the development of neurological disorders, in relation to the aging brain.

Keywords: DNA damage oxidative stress; Neurotoxicity; aging; brain diseases; metal accumulation; mitochondrial dysfunction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Humans
  • Metals, Heavy / toxicity*
  • Nervous System / drug effects*
  • Oxidative Stress


  • Metals, Heavy