Mechanisms associated with the dysregulation of mitochondrial function due to lead exposure and possible implications on the development of Alzheimer's disease

Biometals. 2022 Feb;35(1):1-25. doi: 10.1007/s10534-021-00360-7. Epub 2022 Jan 20.

Abstract

Lead (Pb) is a multimedia contaminant with various pathophysiological consequences, including cognitive decline and neural abnormalities. Recent findings have reported an association of Pb toxicity with Alzheimer's disease (AD). Studies have revealed that mitochondrial dysfunction is a pathological characteristic of AD. According to toxicology reports, Pb promotes mitochondrial oxidative stress by lowering complex III activity in the electron transport chain, boosting reactive oxygen species formation, and reducing the cell's antioxidant defence system. Here, we review recent advances in the role of mitochondria in Pb-induced AD pathology, as well as the mechanisms associated with the mitochondrial dysfunction, such as the depolarisation of the mitochondrial membrane potential, mitochondrial permeability transition pore opening; mitochondrial biogenesis, bioenergetics and mitochondrial dynamics alterations; and mitophagy and apoptosis. We also discuss possible therapeutic options for mitochondrial-targeted neurodegenerative disease (AD).

Keywords: Alzheimer’s disease; Lead toxicity; Mitochondrial dysfunction; Reactive oxygen species; β-Amyloid peptide.

Publication types

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

MeSH terms

  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides
  • Antioxidants
  • Humans
  • Lead / toxicity
  • Mitochondria / pathology
  • Neurodegenerative Diseases* / pathology

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Lead