engleski

Phosphorylated and truncated tau protein in fetal human brain

The microtubule-associated protein tau regulates the dynamic stability of the neuronal cytoskeleton. In fetal human brain only the shortest tau isoform is expressed, while other five isoforms appear postnatally. The activity of tau is controlled mainly by phosphorylation and glycosylation. Tau in a more extensively phosphorylated state is less able to promote microtubule assembly. Due to axonal elongation tau phosphorylation is high in fetal period and decreases with advancing age due to phosphatases activation. However, after about 30 years of age, the plasticity burden in limbic and basal forebrain areas, together with additional genetic and environmental factors that interfere with synaptic plasticity, cause the phosphorylation of tau to increase again. Hyperphosphorylation promotes polymerization of unbound tau and formation of straight and paired helical filaments that form neurofibrillary tangles, dystrophic neurites and neuropil threads. These pathological changes characterize Alzheimer's disease and, to a lesser degree, a number of other neurodegenerative diseases and normal aging. We analyzed postmortal blocks of two fetal brains (11 and 20 weeks of gestation) by using three different monoclonal antibodies (two against phosphorylated epitopes and one that recognizes truncated tau). The left hemispheres were analyzed immunohistochemically, while correspondent areas of the right hemispheres served for Western blot biochemical confirmation. Our preliminary results showed that tau is highly phosphorylated in a manner similar to the phosphorylation state in Alzheimer's disease. The roles of responsible fetal kinases have yet to be described, but may lead to identification of therapeutic targets for halting the progression of paired helical filament formation.

tau protein; fetal brain; phosphorylation

nije evidentirano