No public access
master's thesis
SECRETASE MODULATORS IN HUMAN NEUROBLASTOMA CELLS

Stela Manestar (2016)
Sveučilište u Rijeci
Odjel za biotehnologiju
Metadata
TitlePROBIR MODULATORA GAMA SEKRETAZE U LJUDSKIM STANICAMA NEUROOBLASTOMA
AuthorStela Manestar
Mentor(s)Željko Svedružić (thesis advisor)
Abstract
Značaj: Alzheimerova bolest je neizlječivi neurodegenerativni poremećaj karakteriziran pojavom amiloidnih plakova u moždanom tkivu. Patofiziologija nastanka amiloidnih plakova povezana je sa poremećajem u metabolizmu APP kojeg katalizira γ-sekretaza. Rezultati: U radu su optimizirani različiti postupci razbijanja stanica na dva tipa ljudskih stanica neuroblastoma. Postupak sa deterdžentom Triton X-100 pokazao se najučinkovitijim. Testirani su dva komercijalna ELISA kita za detekciju Aβ 1-40 proteina te je utvrđeno da je IBL ELISA kit učinkovitiji i cjenovno prihvatljiviji. Na kraju je ispitano inhibicijsko djelovanje 4 potencijalna modulatora γ-sekretaze farmaceutske kuće Jiva Pharma Inc. u dvije različite koncentracije na ljudskim stanicama neuroblastoma. Inhibicijsko djelovanje na γ-sekretazu pokazao je JIVA 028 u koncentraciji 1000 μM, a JIVA 004 i 027 su u istoj koncentraciji bili smrtonosni za stanice. JIVA 026 pojačao je aktivnost γ-sekretaze. Zaključak: U radu je utvrđeno da JIVA 028 pri koncentraciji 1000 μM može inhibirati γ-sekretazu, te se JIVA 028 može dalje istraživati kao potencijalni lijek za Alzheimerovu bolest.
Parallel title (English)SECRETASE MODULATORS IN HUMAN NEUROBLASTOMA CELLS
Committee MembersŽeljko Svedružić (committee chairperson)
Jasminka Giacometti (committee member)
Karlo Wittine (committee member)
GranterSveučilište u Rijeci
Lower level organizational unitsOdjel za biotehnologiju
PlaceRijeka
StateCroatia
Scientific field, discipline, subdisciplineBIOTECHNICAL SCIENCES
Biotechnology
Study programme typeuniversity
Study levelgraduate
Study programmeDrug research and development
Academic title abbreviationmag. pharm. inv.
Genremaster's thesis
Language Croatian
Defense date2016-10-27
Parallel abstract (English)
Significance: Alzheimer's disease is a terminal neurodegenerative illness characterized by appearance of amyloid plaques in brain tissue. Pathology of amyloid plaques is linked with disorder in APP metabolism whitch is catalyzed by gamma secretase. Results: In this study several procedures for cell lysis were optimized on two types of human neuroblastoma cells. It was found that the best methods is cell lysis by Triton X-100 detergent. Second, two different commercial ELISA kits for measuring Aβ 1-40 were tested, and results suggest that IBL ELISA kit can satisfy our needs in terms of efficiency and price. Third, 4 compounds as modulators of gamma secretase from Jiva Pharma company were tested. Results show that JIVA 028 can inhibit gamma secretase in concentration 1000 μM. JIVA 004 and 027 are letal to cells at concetration 1000 μM. JIVA 026 activates gamma secretase in tested concentrations. Conclusions: JIVA 028 can inhibit gamma secretase at concentration 1000 μM, and as such can be further analyzed as a potential drug for Alzheimer's disease.
Parallel keywords (Croatian)Alzheimerova bolest gama sekretaza modulator/ Alzheimer disease gamma secretase modulator
Resource typetext
Access conditionNo public access
Terms of usehttp://rightsstatements.org/vocab/InC/1.0/
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:795541
CommitterLea Lazzarich