Utjecaj okadaične kiseline na fosforilaciju proteina tau na epitopima Thr231 i Ser396/Ser404

master's thesis

• Title (english): Effect of okadaic acid on tau protein phosphorylation at Thr231 and Ser396/Ser404 epitopes
• Author: Katarina Pinjušić
• Mentor: Goran Šimić (mentor)
• Mentor: Domagoj Đikić (mentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Božena Mitić (član povjerenstva)
• Committee member: Ivančica Ternjej (član povjerenstva)
• Committee member: Antun Alegro (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2016-02-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Alzheimerova bolest najčešći je uzrok progresivne demencije koju karakterizira sporo napredujući gubitak spoznajnih sposobnosti. Rizik obolijevanja raste gotovo eksponencijalno nakon dobi od 65 godina. Sa sve duljim životnim vijekom ljudi i starenjem stanovništva, Alzheimerova bolest postaje vodeći društveni, ekonomski i medicinski problem, pogotovo kada se zna da još uvijek nema uzročne terapije. Neurofibrilarni snopići jedna su od dvije glavne neuropatološke promjene, a nastaju kao rezultat hiperfosforilacije proteina tau. Tretman kulture stanica ljudskog neuroblastoma SH-SY5Y okadaičnom kiselinom predstavlja potencijalni model za istraživanja fosforilacije proteina tau zahvaljujući mogućnosti proučavanja inhibicije protein fosfataza 1 i 2A. Cilj istraživanja bio je utvrditi utjecaj okadaične kiseline na fosforilaciju proteina tau na epitopima Thr231 i Ser396/404 u kulturi stanica SH-SY5Y i neuronima dobivenim njihovom diferencijacijom. Rezultati su pokazali kako okadaična kiselina nema značajan utjecaj na fosforilaciju epitopa Thr231 i Ser396/S404 u staničnoj liniji SH-SY5Y. Budući da je tretman neurona uzrokovao značajno smanjenje fosforilacije epitopa Ser396/S404, to ukazuje da je fosforilacija navedenog epitopa regulirana nekom fosfatazom koju okadaična kiselina ne inhibira. Pretpostavljeno je da se najvjerojatnije radi o protein fosfatazi 2B. U svrhu stvaranja eksperimentalnog modela za daljnja in vitro istraživanja neuroprotektivnih spojeva za liječenje Alzheimerove bolesti putem sprječavanja hiperfosforilacije proteina tau, pored navedene pretpostavke o fosfatazi 2B, buduća
istraživanja trebala bi utvrditi utjecaj okadaične kiseline i na druge patofiziološki važne epitope proteina tau, kao što su Thr205, Thr212 i Ser409.

Abstract (english)

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.

• Keywords: Alzheimerova bolest; fosforilacija proteina tau; okadaična kiselina
• Keywords (english): Alzheimer's disease; tau protein phosphorylation; okadaic acid
• Language: croatian
• URN:NBN: urn:nbn:hr:217:534964
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-12 08:01:16