prikaz prve stranice dokumenta Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease
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master's thesis
Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease
2022. urn:nbn:hr:193:119946
Tić, Iva
University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

Tić, I. (2022). Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease (Master's thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:119946

Tić, Iva. "Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease." Master's thesis, University of Rijeka, 2022. https://urn.nsk.hr/urn:nbn:hr:193:119946

Tić, Iva. "Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease." Master's thesis, University of Rijeka, 2022. https://urn.nsk.hr/urn:nbn:hr:193:119946

Tić, I. (2022). 'Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease', Master's thesis, University of Rijeka, accessed 24 April 2024, https://urn.nsk.hr/urn:nbn:hr:193:119946

Tić I. Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease [Master's thesis]. Rijeka: University of Rijeka; 2022 [cited 2024 April 24] Available at: https://urn.nsk.hr/urn:nbn:hr:193:119946

I. Tić, "Connection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease", Master's thesis, University of Rijeka, Rijeka, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:193:119946

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Metadata
TitleConnection between microbiome and neurodegenerative diseases: how microbiota-derived prions can affect development of Alzheimer’s disease
Title (croatian)Povezanost mikrobioma i neurodegenerativnih bolesti: kako prioni izolirani iz mikrobioma utječu na razvoj Alzheimerove bolesti
AuthorIva Tić
MentorNatalia Sanchez de Groot (mentor)
MentorŽeljka Minić (komentor)
Committee memberChristian Andrew Reynolds (predsjednik povjerenstva)
Committee memberElitza Petkova Markova - Car (član povjerenstva)
Committee memberŽeljka Minić (član povjerenstva)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2022-09-26, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Molecular Biotechnology
Abstract
The idea that Alzheimer’s disease (AD) has an origin in the gut has been widely accepted based on crosstalk between microbiota, gut and brain. To the hypothesis of the present work, gut microbiota could be a source of a major number of amyloids. This work used two of the best studied bacterial amyloids; (i) curli, produced by Escherichia coli and (ii) Sup35p, produced by Saccharomyces cerevisiae. Curli has beneficial roles for bacteria by helping them to form biofilms and to resist destruction by physical or immune factors, while at the same time share similarities inside tertiary structure with central nervous system’s (CNS) amyloids that are responsible for forming toxic Aβ plaques in AD. Under certain circumstances bacterial derived amyloids can leak from GI tract and accumulate at the systemic and brain level. In order to discern which peptides from human microbiome are able to influence human proteins aggregation, this work implemented proteome-wide bioinformatic tools and in vitro assays to follow which putative amyloid core sequence can lead the formation of amyloid aggregates and the cell-to-cell transmission of the aggregated conformation. Production of amyloid fibrils through CDAG system based on curli was achieved with all 12 tested peptides and their existence was proved by phenotype evaluation in the liquid and on plates containing the amyloid binding dye (Congo red, CR) as well as under Transmission electron microscopy (TEM). The Sup35p prion system, that regulates translation termination in Saccharomyces cerevisiae was used to test the ability of the amyloid cores, to propagate the amyloid aggregated conformation between yeast cells. Finally, bacterial and yeast systems provided simplified models for studying the conserved mechanisms of amyloid formation, degradation, and function as well as connection between bacterial amyloids and amyloid structures in brain formed during neurodegeneration.
Abstract (croatian)
Unatrag nekoliko godina povezanost intestinalnog sustava s nastankom neurodegenerativnih bolesti kao što je Alzheimer postaje sve istraženije područje temeljeno na komunikaciji između mozga i crijevnog sustava te crijevnog mikrobioma. Prema hipotezi ovog rada, crijevni mikrobiom čini potencijalni rezervoar velike količine amiloida. Shodno tome, u ovom radu su korištena dva najbolje proučena amiloida; (i) curli, koje proizvodi Escherichia coli te (ii) Sup35p, koje proizvodi Saccharomyces cerevisiae. Curli imaju korisnu ulogu u formiranju bakterijskog biofilma i zaštiti od fizičkih ili imunoloških oštećenja stanice, dok istovremeno dijele sličnosti s tercijarnom strukturom amiloida koji se nakupljaju u središnjem živčanom sustavu čineći toksične Aβ plakove- jedne od glavnih patoloških markera Alzheimerove bolesti. Pod određenim okolnostima amiloidi bakterijskog podrijetla mogu „curiti“ iz gastrointestinalnog (GI) trakta i akumulirati se u mozgu. Kako bi se razlučilo koji peptidi izolirani iz ljudskog mikrobioma mogu utjecati na agregaciju ljudskih proteina, ovaj rad implementirao je bioinformatičke alate za analizu cijelog proteoma te in vitro ispitivanja kako bi se utvrdilo koja sekvenca amiloidne jezgre može dovesti do stvaranja amiloidnih nakupina i prijenosa agregiranih konformacija s jedne na drugu stanicu. Proizvodnja amiloidnih fibrila putem CDAG sustava postignuta je kod svih 12 testiranih peptida, a njihov potencijal je dokazan procjenom fenotipa na mikrobiološkim pločama i u tekućini koje sadrže boju za vezanje amiloida (engl. Congo red, CR). Proizvodnja amiloidnih agregegata je također vizualizirana transmisijskom elektronskom mikroskopijom (TEM). Sup35p prionski sustav, koji regulira prekid translacije u Saccharomyces cerevisiae, korišten je za testiranje sposobnosti amiloidnih jezgri da propagiraju amiloidne nakupine između stanica kvasca. Zaključno, sustavi bakterija i kvasaca omogućili su proučavanje očuvanih mehanizama stvaranja, razgradnje i funkcije amiloida te promaknuli saznanja o povezanosti bakterijskih amiloida s amiloidnim formacijama koje nastaju tijekom neurodegeneracije.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:193:119946
Study programmeTitle: Drug research and development
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra istraživanja i razvoja lijekova (magistar/magistra istraživanja i razvoja lijekova)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-09-25 15:17:12