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Lead and Excitotoxicity

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Handbook of Neurotoxicity

Abstract

Lead (Pb2+) is a known neurotoxicant, but the mechanism of its neurotoxicity is not clearly understood. Several biochemical alterations have been shown to be caused by Pb2+ exposure in mammalian brain, but none of these changes alone can explain the mechanism of Pb2+-induced impairment of learning and memory. The most mechanistically relevant biochemical abnormalities that are directly involved in learning and memory are the excitotoxic effects caused by modulation of the N-methyl-d-aspartate-type glutamate receptors (NMDAR) in glutamatergic synapses. Pb2+ is known to affect not only the expression of the different subunits of the NMDARs but also the ontogenic developmental switch of the various NMDAR subunits that is essential for learning and memory. Overactivation of serine/threonine protein phosphatases (PPs) appears to be involved in these synaptic changes. PPs may not only affect the functions of the various subunits of the NMDAR directly by modulating the phosphorylation state of these subunits but may also affect their downstream function by modulation of the phosphorylation state of the downstream effectors like the cyclic AMP response element binding protein (CREB) and other proteins involved in this process. There is a great need to put these isolated pieces of information together and workout the exact pathway(s) that are disturbed by Pb2+.

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Rahman, A. (2014). Lead and Excitotoxicity. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_142

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