FIG. 8.

Pb neurotoxicity and synaptic signaling. (a) Pb enters cells due to its ability to mimic Ca²⁺ and Fe²⁺ ions. (b) Inside the cell, Pb can trigger oxidative stress by different mechanisms, including the accumulation of ALA; the formation of Pb²⁺–O₂^•− complexes; and the release of labile Fe²⁺ from Ft. (c) Pb can also form complexes with GSH [Pb(GSH_2–3)] and bind to protein thiols. (d) Mitochondrial dysfunction and oxidative stress induced by Pb have also been linked to MCU. (e) Pb can displace Zn²⁺ and impair Zn²⁺ binding protein function. Furthermore, Pb interferes with the Se-dependent redox processes. (f) Finally, Pb can prevent CaM activation and thus reduce NOS activity. ALA, aminolevulinic acid; CaM, Ca²⁺/calmodulin; NOS, nitric oxide synthase; O₂^•−, superoxide anion radical; Pb, lead; Se, selenium.