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Molecular targets of lead in brain neurotoxicity

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Abstract

The detrimental effects of lead poisoning have been well known since ancient times, but some of the most severe consequences of exposure to this metal have only been described recently. Lead (Pb2+) affects the higher functions of the central nervous system and undermines brain growth, preventing the correct development of cognitive and behavioral functions. As an established neurotoxin, Pb2+ crosses the blood-brain barrier rapidly and concentrates in the brain. The mechanisms of lead neurotoxicity are complex and still not fully under-stood, but recent findings recognized that both Ca2+-dependent proteins and neurotransmitters receptors represent significant targets for Pb2+. In particular, acute and chronic exposure to lead would predominantly affect two specific protein complexes: protein kinase C and theN-methyl-D-aspartate subtype of glutamate receptor. These protein complexes are deeply involved in learning and cognitive functions and are also thought to interact significantly with each other to mediate these functions. This review outlines the most recent hypotheses and evidences that link lead poisoning to impairment of these protein functions, as well as thein vitro experimental approaches that are most likely to provide information on basic mechanicistic processes.

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  1. Istituto di Biofisica, Sezione di Genova, Consiglio Nazionale delle Ricerche, via De Marini, 6-16149, Genova, Italy

    Carla Marchetti

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Marchetti, C. Molecular targets of lead in brain neurotoxicity. neurotox res 5, 221–235 (2003). https://doi.org/10.1007/BF03033142

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