No public access
master's thesis
Screening of novel drugs for Alzheimer diseasein human neuroblastoma cells

Marta Hlača (2016)
University of Rijeka
Department of Biotechnology
Metadata
TitleProbir lijekova za Alzheimerovu bolest u ljudskim stanicama neuroblastoma
AuthorMarta Hlača
Mentor(s)Željko Svedružić (thesis advisor)
Abstract
ZNAČAJ: Alzheimerova bolest je jedna od najskupljih bolesti današnjice za sustav zdravstvene zaštite u razvijenim zemljama. Postojeći lijekovi samo ublažavaju simptome, a glavna meta tih lijekova je izuzetno složen enzim, intramembranska proteaza γ sekretaza. REZULTATI: U ovom radu razvijen je ELISA protokol za mjerenje količine unutarstaničnog amiloid β peptida iz ljudskih stanica neuroblastoma SH-SY5Y APPwt A9 5x. Koristeći razvijeni protokol napravljen je probir između 5 potencijalnih lijekova za Alzheimerovu bolest. Najboljim inhibitorom γ sekretaze pokazao se JIVA 28, jer ne mijenja morfologiju stanica niti utječe na njihovu smrtnost, a dobro je topljiv u DMSO i ne mijenja svoje agregacijsko stanje. Potencijalni lijek JIVA 39 netopljiv u uvjetima u kojima rastu stanice, dok potencijalni lijekovi JIVA 4, JIVA 40 i JIVA 41 nisu pokazali inhibiciju γ sekretaze. Također, JIVA 40 je bio smrtonosan za stanice. ZAKLJUČAK: Nakon inkubacije s potencijalnim lijekovima za Alzheimerovu bolest mjerena je količina unutarstaničnog Aβ iz ljudskih stanica neuroblastoma novim razvijenim ELISA protokolom. Rezultati ukazuju da je JIVA 28 jedini inhibitor γ sekretaze, jer istovremeno nije smrtonosan za stanice i ne mijenja njihovu morfologiju što ga čini jedinim potencijalnim lijekom za Alzheimerovu bolest.
KeywordsAlzheimer's disease γ secretase amyloid β peptide sandwich ELISA new drugs design
Parallel title (English)Screening of novel drugs for Alzheimer diseasein human neuroblastoma cells
Committee MembersŽeljko Svedružić (committee chairperson)
Jasminka Giacometti (committee member)
Karlo Wittine (committee member)
GranterUniversity of Rijeka
Lower level organizational unitsDepartment of Biotechnology
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 date2016-10-26
Parallel abstract (English)
SIGNIFICANCE: Alzheimer’s disease is one of the most expensive diseases of today for health care system in developed countries. Present drugs only relief the symptoms and their main target is an extremely complex enzyme, intramembrane protease y secretase. RESULTS: In our study a new ELISA protocol was developed for measuring the amount of intracellular amyloid β peptide from human neuroblastoma cells SH-SY5Y APPwt A9 5x. New developed protocol was used for screening of 5 potential drugs for Alzheimer’s disease. Best inhibitor of γ secretase is JIVA 28 because it doesn’t change the morphology of cells and isn’t lethal for cells while it is soluble in DMSO and doesn’t change its state of aggregation. Potential drug JIVA 39 isn’t soluble under conditions for cell growth and potential drugs JIVA 4, JIVA 40 and JIVA 41 didn’t show inhibition of γ secretase. Also, JIVA 40 was lethal for cells. CONCLUSION: After incubation with potential drugs for Alzheimer’s disease the amount of intracellular Aβ from human neuroblastoma cells was measured with new developed ELISA protocol. Results indicate that only JIVA 28 inhibits y secretase and at the same time isn’t lethal or changes the morphology of the cells making it a potential drug for Alzheimer’s disease.
Parallel keywords (Croatian)Alzheimerova bolest γ sekretaza amiloid β peptid sandwich ELISA dizajn novih lijekova
Resource typetext
Access conditionNo public access
Terms of usehttp://rightsstatements.org/vocab/InC/1.0/
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:056747
CommitterLea Lazzarich