13.10 – Protein Phosphatase 1 as a Potential Mediator of Aluminum Neurotoxicity

Reversible protein phosphorylation is a ubiquitous and universal process generally regarded as the major posttranslational modification through which numerous physiological processes are regulated (Cohen 2002a; de la Fuente van Bentem et al. 2008). It is a dynamic process whereby phosphate groups are incorporated into proteins by protein kinases and removed by protein phosphatases. Thus, protein phosphorylation is a reversible process that alters the function and/or localization of target proteins and in this fashion controls various biological functions. In turn, the protein kinases and protein phosphatases, which are particularly abundant and diverse in mammalian brain, are themselves regulated by a myriad of extracellular and intracellular signals. Many of the complex functions of the mammalian central nervous system are regulated by phosphorylation/dephosphorylation of key regulatory proteins. Many extracellular messengers exert their effects in the central nervous system by modulating the intracellular concentration of specific second messengers, which in turn lead to the activation/inhibition of specific protein kinases and phosphatases. As a result, abnormal phosphorylation of key regulatory proteins has been associated with a variety of disease conditions and dysfunctional states. Defects in protein phosphorylation mechanisms operating in the mammalian central nervous system may be a common feature of many neurological and chemical-induced disease states (Gong and Iqbal 2008; Lee and Messing 2008).