oa Lead (Pb²⁺) neurotoxicity: Ion-mimicry with calcium (Ca²⁺) impairs synaptic transmission. A review with animated illustrations of the pre- and post-synaptic effects of lead

Lead (Pb²⁺) is ubiquitously distributed in the environment and shows significant health effects in humans, especially in the nervous system. In this review we illustrate how (Pb²⁺) neurotoxicity is associated with its ability to partially mimic the function of Ca²⁺ and modifies synaptic transmission pre- and post-synaptically. As Pb²⁺ binds to calcium-binding sites it alters their functionality, ranging from reduced currents through voltage and receptor gated channels, to modulation of ion-transporters and alterations of calcium-dependent signaling pathways. Overall Pb²⁺ exposure not only reduces pre-synaptically the transmitter release, but also post-synaptically the likelihood to generate a new action potential. This review will highlight the major-interactions with the different targets in schemes and short animated sequences to allow a general understanding of lead neurotoxicity to a wider audience; therefore, not all possible mechanisms will be mentioned or discussed.