Naslov
Phosphorylation of tau proteins in development and Alzheimer's disease

Autori
Mladinov, Mihovil ; Boban, Marko ; Boban, Marina ; Grbić, Kristina ; Mimica, Ninoslav ; Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Neurologia Croatica 55 (Suppl. 4) - Book of Abstracts / Šimić, Goran ; Mimica, Ninoslav - Zagreb : Denona, 2006, 66-66

Skup
3rd Croatian Congress on Alzheimer's disease with international participation

Mjesto i datum
Brijuni, Hrvatska, 07.09.2006. - 10.09.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
phosphorylation; tau proteins; fetal development; Alzheimer's disease; magnetic resonance imaging; early diagnosis

Sažetak
Tau proteins belong to the microtubule-associated proteins (MAP) and are crucially involved in microtubule assembly, stabilization and cytoskeleton maintenance. Tau proteins also allow microtubules to interconnect with other cytoskeletal components and regulate their growing dynamics. The biological activity of tau is controlled mostly by phosphorylation and, to a lesser degree, by glycosylation. Phosphorylation of tau proteins is developmentally regulated. It is high in fetal period and decreases with age. A single gene on the long arm of chromosome 17 encodes the human tau protein. Its primary transcript contains 13 exons. In adult human brain, six tau isoforms are expressed by alternative splicing of exons 2, 3 and 10. The isoforms length range from 352 to 441 aa. The unique expression pattern of tau isoforms in humans could represent a link to the particular vulnerability of humans to neurodegenerative disorders, particularly Alzheimer's disease (AD). Brain neurodegenerative disorders characterized by intraneuronal and glial fibrillar lesions formed by tau proteins are known as tauopathies. Tau proteins from these lesions are abnormally phosphorylated, which is probably the most important cause of their aggregation. There have been many attempts to find an accurate biomarker in the cerebrospinal fluid (CSF) for the diagnosis of neurodegenerative diseases. Phosphorylated tau as a marker for AD came closest to this aim. The main long-term goals of the project in our laboratory are: 1) to determine how abnormalities of the selected phospho-tau epitopes 181, 199, 202/205, 231, 396/404 and 422, ratio of 3R/4R tau isoforms and total tau in CSF, as revealed by enzyme- linked immunosorbent assay (ELISA), Western blot and eventually 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 the tau phosphorylation in AD and to test the presumed protective action of fetal tau isoform (which has only 3 microtubule binding domains - 3R) on tau polymerization in neuronal cell culture. Through fulfillment of these goals, we expect to obtain new knowledge relevant for tracking the progression of neurofibrillary degeneration and early detection of AD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
Indexed / Abstracted in: Neuroscience Citation Index ; EMBASE / Excerpta Medica

POVEZANOST RADA