Seeding and structural varibility in α-synucleinopathies

Candelise, Niccolò

Seeding variability of different alpha-synuclein strains

dc.contributor.advisor	Zerr, Inga Prof. Dr.
dc.contributor.author	Candelise, Niccolò
dc.date.accessioned	2019-06-12T13:51:07Z
dc.date.available	2019-06-12T13:51:07Z
dc.date.issued	2019-06-12
dc.identifier.uri	http://hdl.handle.net/21.11130/00-1735-0000-0003-C12C-2
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-7350
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Seeding and structural varibility in α-synucleinopathies	de
dc.title.alternative	Seeding variability of different alpha-synuclein strains	de
dc.type	doctoralThesis	de
dc.contributor.referee	Bähr, Mathias Prof. Dr.
dc.date.examination	2019-03-08
dc.description.abstracteng	In the present work, we were interested in applying the Real-time quaking-induced conversion (RT-QuIC) for the detection of the seeding activity of Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) brain derived α-synuclein seeds. and analyzing the structure and morphology of the α-synuclein aggregates generated via RTQuIC. A different seeding and conversion ability support the existence of α-synuclein conformational variants in both α-synucleinopathies. To this aim, brain materials derived from neuropathologically well-characterised cases with DLB, PD and controls have been processed by filtration and centrifugation steps to obtain an α-synuclein seeding competent fraction, deployed as seed for the RT-QuIC. Biochemical and morphological analyses of RT-QuIC products were conducted by western blot, dot blot analysis, Raman spectroscopy, atomic force microscopy and transmission electron microscopy analyses. We observed a different seeding activity between DLB and PD, which resulted in the generation of a PK-resistant and fibrillary α- synuclein species in DLB seeded reactions, while PD and control seeds failed in the conversion of wild type α-synuclein substrate. The structural variance between DLB and PD seeding kinetics and products indicated the existence of different α-synuclein stains in these groups. Our study contributes to the understanding of the clinical heterogeneity observed among α-synucleinoèpathies and opens news avenues for the future development of strain-specific therapies. !	de
dc.contributor.coReferee	Outeiro, Tiago Fleming Prof. Dr.
dc.contributor.thirdReferee	Flügel, Alexander Prof. Dr.
dc.subject.eng	α-synuclein	de
dc.subject.eng	RT-QuIC	de
dc.subject.eng	Parkinson's Disease	de
dc.subject.eng	Dementia with Lewy Bodies	de
dc.identifier.urn	urn:nbn:de:gbv:7-21.11130/00-1735-0000-0003-C12C-2-8
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	1667339451

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