Cellular mechanisms of lead neurotoxicity

Med Sci Monit. 2006 Mar;12(3):RA57-65. Epub 2006 Feb 23.


Lead (Pb2+), a heavy metal, has been used by humans for many technological purposes, which is the main reason for its present widespread distribution. Although various actions have been taken to decrease the use and distribution of lead in the environment, it remains a significant health hazard. The toxic mechanism of lead is caused by its ability to substitute for other polyvalent cations (particularly divalent cations, such as calcium [Ca2+] and zinc [Zn2+]) in the molecular machinery of living organisms. These interactions allow lead to affect different biologically significant processes, including metal transport, energy metabolism, apoptosis, ionic conduction, cell adhesion, inter- and intracellular signaling, diverse enzymatic processes, protein maturation, and genetic regulation. Membrane ionic channels and signaling molecules seem to be one of the most relevant molecular targets contributing to lead's neurotoxicity; the developing central nervous system is particularly susceptible. At critical times in development, lead may have a disorganizing influence with long-lasting effects that may continue into teenage years and beyond. Pediatric lead poisoning is more common than adult lead poisoning, and its effects may occur at reduced blood levels with subclinical symptoms, thus a high index of suspicion is necessary for physicians when dealing with pediatric patients. Long-term effects of lead poisoning may produce cognitive and motor impairment, with behavioral alterations. This review is centered on the description of the molecular mechanisms of lead toxicity and its repercussions on cellular functions.

Publication types

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

MeSH terms

  • Calcium / metabolism
  • Calcium Channels / toxicity
  • Humans
  • Lead / metabolism*
  • Lead / toxicity*
  • Lead Poisoning / metabolism*
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / metabolism
  • Zinc / metabolism


  • Calcium Channels
  • Lead
  • Zinc
  • Calcium