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Protein phosphatases: enzymes that catalyse the hydrolysis of esters of phosphoric acid, resulting in Sodium salicylate removal of phosphate groups from proteins.Tauopathy: neurodegenerative disease in which intracellular pathological aggregates of tau protein are present in brain.Absence of E and E gives rise to N tau isoforms, whereas inclusion of E produces N and inclusion of both E and E results in N tau isoforms.MM represent the four imperfectrepeat microtubulebinding domains, M being encoded by exon. Lack of M produces R tau and inclusion results in R tau isoforms.The prolinerich domain in the centre of the tau polypeptide is indicated.Alternativesplicing produces tau isoforms ranging in size from amino acids.Six of the phosphorylation sites have been identified only by phosphospecific antibody labelling; the remaining phosphorylation sites have been identified by direct means. Within neurons, tau is found predominantly in axons, where it exists as a highly soluble, phosphorylated protein that stabilizes and promotes the polymerization of microtubules principally through the microtubulebinding domain.By contrast, all six tau isoforms are present in mature brain, and phosphorylation of these tau species is Choline chloride relatively reduced compared to that in foetal brain.Such developmentally regulated changes in tau are likely to be related to an increased requirement for neuronal plasticity during embryogenesis and early development.Increased tau phosphorylation reduces the amount of microtubulebound tau, and R tau isoforms also bind less tightly than R tau to microtubules.These factors thus support the notion that the requirement for increased plasticity can be met by elevated phosphorylation of R tau during periods of prolic synaptogenesis.Furthermore, reduced plasticity is apparent in fully differentiated adult neurons in which R tau isoforms are also expressed and tau phosphorylation is decreased. Phosphorylation in the microtubulebinding domain of tau is believed to be crucial in regulating microtubule stabilization.In particular, phosphorylation of the orthologous residues in adjacent microtubulebinding repeats at S and S has been suggested to detach tau from microtubules. Phosphorylation of tau at sites distinct from the microtubulebinding domain might also be involved in regulation of cytoskeletal stability because S and T in tau also reduce its ability to bind to microtubules. However, the relative importance of specic individual phosphorylation sites or subsets of phosphorylation sites for tau function andor pathogenesis remains to be rmly established.Conversely, elevated tau expression enhances susceptibility to toxic stimuli andor neurodegeneration and also results in increased production of neurotoxic amyloidogenic peptides. Based on reactivity to phosphospecic tau antibodies, the pattern of tau phosphorylation in the various tauopathies seems to be similar irrespective of the underlying cause of the pathology.Tau abnormalities, whether they are due to mutations in the tau gene causing amino acid changes or an altered R:R tau ratio, cause deposition in the brain of highly phosphorylated tau in an aberrant conformation.However, as mentioned above, although intracellular accumulations of phosphorylated tau have been assumed to be harmful to cells, an alternative role is one of protection against toxic events.An increase in the steadystate level of tau might result in excess cytoplasmic tau becoming deposited in insoluble intracellular inclusions in an effort to restore to physiological levels the amount of tau available for microtubule binding in neurons.

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