Neurotoxicity of lead. Hypothetical molecular mechanisms of synaptic function disorders.

Lead (Pb) toxicity is still a major health problem associated with both environmental and occupational exposure. Special attention is given to the neurotoxic effect of lead. Along with the newly emerging data, the Pb concentration in the body that can be considered safe is declining. Numerous studies on the neurotoxicity of Pb have shown multiple cellular 'molecular targets' of this metal at the biochemical and molecular levels, and differences in sensitivity to its toxic action among various neural cells. One possible target of the neurotoxic effect of Pb (at the synapse level) is N-methyl-D-aspartic acid (NMDA) receptors. This review presents the hypothetical molecular mechanism by which Pb disrupts synapse formation and plasticity in developing hippocampal neurons and the role of the NMDA receptor-dependent signaling pathway and brain-derived neurotrophic factor (BDNF) as a mechanism of Pb neurotoxicity at the synapse level.