engleski

Tau protein isoforms and phosphorylation in development and Alzheimers disease

Tau proteins belong to the microtubule-associated proteins (MAP) group and are involved in microtubule assembly, stabilization and cytoskeleton maintenance. The biological activity of tau is controlled mostly by phosphorylation and is developmental^ regulated. It is high in the fetal period and decreases with age. A single gene on chromosome 17 encodes the human tau protein. In the adult human brain, six tau isoforms are expressed. The unique expression pattern of human tau isoforms could represent a link to the particular vulnerability of humans to neurodegenerative disorders, particularly Alzheimer's disease (AD). AD is characterized by intraneuronal and glial fibrillar lesions formed by tau proteins, which are abnormally phosphorylated. Phosphorylation of tau proteins is probably the most important cause of their aggregation. Phosphorylated tau is the most accurate biomarker in the cerebrospinal fluid (CSF) for the diagnosis of AD. The main goals of the project in our laboratory are: 1. to determine how abnormalities of selected phospho-tau epitopes 181, 199, 202/205, 231, 396/404 and 422, ratio of 3R/4R tau isoforms and the total tau in CSF, as revealed by enzyme-linked immunosorbent assay (ELISA), Western blot and mass spectrometry, relate to alterations in glutamatergic transmission, MRI-determined entorhinal and hippocampal atrophy and cognitive changes ; 2. to identify and evaluate the possible role of reactivated fetal kinases in tau phosphorylation in AD, and to test the presumed protective action of fetal tau isoform on tau polymerization in neuronal cell culture. We expect to obtain new knowledge relevant for tracking the progression of neurofibrillary degeneration and early detection of AD.

tau proteins ; Alzheimers disease ; phosphorylated tau

Sažetak je osim na engleskom naveden i na njemačkom jeziku