Interaction of Parkinson s disease protein alpha-synuclein with lipid membranes

master's thesis

• Title (croatian): Interakcija Parkinsonovog proteina alfa-sinukleina sa lipidnim membranama
• Author: Mateja Gulija
• Mentor: Lidija Barišić (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Organic Chemistry); Zagreb
• Defense date and country: 2018-12-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Alpha-synuclein is a soluble synaptic protein whose aggregation resulting in amyloid Lewy bodies formation within neurons is a pathological characteristic of Parkinson’s disease. It is believed that the interaction of alpha-synuclein with synaptic lipid vesicles is related to the protein function. The aim of this thesis is to characterize the interaction of alpha-synuclein with negatively charged vesicles of 1,2-dioleoyl–phosphatidyl-glycerol (DOPG) and 1,2-dioleoyl- phosphatidyl-serine (DOPS) and the consequences of such interactions on alpha-synuclein amyloid formation by using biophysical methods. It was detected that alpha-synuclein to phospholipid ratio modulates the kinetics of the protein aggregation. High concentrations of lipids (lipid:protein molar ratio above 40) induced alpha-helical structure in alpha-synuclein and repressed the protein aggregation whereas at low concentrations of lipids, alpha-synuclein has shown partial folding and fibril formation was stimulated.

Abstract (english)

Alfa-sinuklein je topljivi sinaptički protein čija je agregacija, kojom dolazi do tvorbe amiloidnih Lewy tijela unutar neurona, patološka karakteristika Parkinsonove bolesti. Vjeruje se da interakcija alfa-sinukleina sa sinaptičkim lipidnim vezikulama ima utjecaj na funkciju proteina. Cilj ovog rada je karakterizirati interakciju alfa-sinukleina s negativno nabijenim vezikulama priređenima iz 1,2-dioleoil-fosfatidil-glicerola (DOPG) i 1,2-dioleoil-fosfatidil-serina (DOPS) te posljedice takvih interakcija na formiranje alfa-sinuklein amiloida upotrebom biofizikalnih metoda. Otkriveno je da omjer alfa-sinukleina prema fosfolipidima modulira kinetiku agregacije alfa-sinukleina. Visoke koncentracije lipida (omjer lipida i proteina iznad 40) dovele su do tvorbe heličnih struktura i ograničenja fibrilacije alfa-sinukleina, dok je pri niskoj koncentraciji lipida, alfa-sinuklein pokazao djelomično smatanje te je stimulirano stvaranje fibrila.

• Keywords: alpha-synuclein; Parkinson's disease; protein aggregation; liposomes; biophysical methods
• Keywords (english): alfa-sinuklein; Parkinsonova bolest; agregacija proteina; liposomi; biofizikalne metode
• Language: english
• URN:NBN: urn:nbn:hr:159:624427
• Study programme: Title: Bioprocess Engineering; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva (magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2019-11-14 13:07:03