Nanobody-basierter Sensor für die Zell-zu-Zell-Übertragung von α-Synuclein bei Morbus Parkinson

Gerdes, Christoph

dc.contributor.advisor	Rizzoli, Silvio O. Prof. Dr.
dc.contributor.author	Gerdes, Christoph
dc.date.accessioned	2021-05-18T06:15:54Z
dc.date.available	2022-11-23T00:50:08Z
dc.date.issued	2021-05-18
dc.identifier.uri	http://hdl.handle.net/21.11130/00-1735-0000-0008-5827-A
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-8594
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Nanobody-basierter Sensor für die Zell-zu-Zell-Übertragung von α-Synuclein bei Morbus Parkinson	de
dc.type	doctoralThesis	de
dc.title.translated	Nanobody-based sensor for cell-to-cell transmission of α-synuclein in Parkinson's disease	de
dc.contributor.referee	Rizzoli, Silvio O. Prof. Dr.
dc.date.examination	2021-05-25
dc.description.abstracteng	Aggregation and cell-to-cell transmission of α-Synuclein (αSyn) are hallmarks of several neurodegenerative diseases, including Parkinson's disease. In this work, it is shown that the nanobody NbSyn87, previously described to bind αSyn, also shows cross-reactivity for the proteasomal subunit Rpn10. This feature was exploited to design a new sensor for αSyn by fusing NbSyn87 to GFP and a nuclear localization signal. Therefore, when expressed in cells, the sensor is degraded by the proteasome in absence of αSyn but stabilized in presence of αSyn. This results in fluorescence signal fluctuations depending on the presence of intracellular αSyn. In this work, the biosensor is characterized in cells and shows that it is a sensitive sensor which specifically binds to human αSyn. Using the sensor, it is demonstrated that αSyn enters cells more efficiently when bound to a lipid layer. Finally, the sensor reveals the presence of transmittable αSyn in human cerebrospinal fluid. Thus, the sensor might be used to develop a diagnostic tool for synucleinopathies.	de
dc.contributor.coReferee	Outeiro, Tiago Fleming Prof. Dr.
dc.contributor.thirdReferee	Oppermann, Martin Prof. Dr.
dc.subject.eng	Parkinson	de
dc.subject.eng	alpha-Synuclein	de
dc.subject.eng	transmission	de
dc.subject.eng	nanobody	de
dc.subject.eng	synucleinopathies	de
dc.subject.eng	CSF	de
dc.subject.eng	prion	de
dc.subject.eng	synuclein	de
dc.subject.eng	neurophysiology	de
dc.subject.eng	neurodegeneration	de
dc.identifier.urn	urn:nbn:de:gbv:7-21.11130/00-1735-0000-0008-5827-A-3
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Neurologie - Allgemein- und Gesamtdarstellungen (PPN619876247)	de
dc.subject.gokfull	Physiologie / Pathophysiologie - Allgemein- und Gesamtdarstellungen (PPN619875283)	de
dc.description.embargoed	2022-11-23
dc.identifier.ppn	1758126787

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Human- und Zahnmedizin [2872]

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