Effect of okadaic acid on tau protein phosphorylation at Thr231 and Ser396/Ser404 epitopes

Pinjušić, Katarina (2016) Effect of okadaic acid on tau protein phosphorylation at Thr231 and Ser396/Ser404 epitopes. Diploma thesis, Faculty of Science > Department of Biology.

Language: Croatian

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Alzheimer's disease is the most common cause of progressive dementia characterized by a slowly progressive cognitive impairment. Over the age of 65, the risk of developing Alzheimer's disease increases almost exponentially with age. With the increase of life expectancy and number and proportion of older people in the population, Alzheimer's disease is becoming a leading social, economic and medical problem, especially in regard to lack of causal therapy. Neurofibrillary tangles are one of the two major neuropathological lesions, resulting from hyperphosphorylation of tau protein. As okadaic acid, by inhibiting protein phosphatase 1 and 2A, induces tau phosphorylation in SH-SY5Y human neuroblastoma cell culture, this system represents a potential model for study of tau protein phosphorylation. The aim of this study was to determine the effect of okadaic acid on tau protein phosphorylation at epitopes Thr231 and Ser396/404 in SH-SY5Y cell culture and neurons derived thereof. The results showed that okadaic acid had no significant effect on phosphorylation of Thr231 epitope and epitope Ser396/S404 in SH-SY5Y cell line. However, treatment of neurons induced a significant reduction in phosphorylation of epitope Ser396/S404, suggesting that phosphorylation of that epitope is regulated by some phosphatase that is not inhibited by okadaic acid, most probably protein phosphatase 2B. In order to establish an experimental model for further in vitro research of neuroprotective compounds for treatment of Alzheimer's disease by preventing the hyperphosphorylation of tau protein, besides the role of protein phosphatase 2B, it will be also important to determine the effect of okadaic acid on other phospho-tau epitopes, such as Thr205, Thr212 and Ser409.

Item Type: Thesis (Diploma thesis)
Keywords: Alzheimer's disease, tau protein phosphorylation, okadaic acid
Supervisor: Šimić, Goran
Co-supervisor: Đikić, Domagoj
Date: 2016
Number of Pages: 48
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 24 Mar 2016 15:31
Last Modified: 24 Mar 2016 15:31
URI: http://digre.pmf.unizg.hr/id/eprint/4626

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