Einfluss des Proteinaggregationshemmstoffs anle138b auf Beginn und Verlauf der Amyotrophen Lateralsklerose im transgenen hSOD1-Mausmodell

Thyssen, Stella

dc.contributor.advisor	Weishaupt, Jochen Prof. Dr.
dc.contributor.author	Thyssen, Stella
dc.date.accessioned	2014-05-06T08:42:05Z
dc.date.available	2014-07-01T22:50:05Z
dc.date.issued	2014-05-06
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0022-5EA3-0
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-4474
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-4474
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Einfluss des Proteinaggregationshemmstoffs anle138b auf Beginn und Verlauf der Amyotrophen Lateralsklerose im transgenen hSOD1-Mausmodell	de
dc.type	doctoralThesis	de
dc.title.translated	Influence of the protein aggregation inhibitor anle138b on the beginning and progression of amyotrophic lateral sclerosis in the transgenic hSOD1 mouse model	de
dc.contributor.referee	Weishaupt, Jochen Prof. Dr.
dc.date.examination	2014-06-24
dc.description.abstracteng	1. Review Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which the degeneration of the first and the second motor neuron is responsible for spastic and atonic paresis. The incidence of ALS is 2 of 100 000 people per year and is therefore the most common motor neuron disease with a very severe prognosis of only three to five years medium duration of disease. However, there has been no solution of the pathomechanism and a causal therapy of ALS yet. But there is a familiar form of ALS with a genetic background that is in charge of ten percent of ALS cases (familiar ALS). With 10 to 20% of fALS cases, mutations of the gen of the protein superoxiddismutase 1 (SOD1) are the most frequent ones. The cause of the other 90% of ALS cases is unknown (sporadic ALS). There are a lot of different hypotheses explaining the pathophysiological mechanisms of the degeneration of the motor neurons. One of these hypotheses is the protein aggregation hypothesis in which aggregation and accumulation of different proteins are said to be the reason for the degeneration of the motor neurons. Especially familiar SOD1-associated ALS is marked by protein aggregates which is the basis of this hypothesis. 2. Design of study For testing the hypothesis of protein aggregation as a possible cause of ALS and potentially developing a new therapy for ALS, the protein aggregation inhibitor anle138b was analysed by use of the hSOD1 mouse mode for ALS in this study. For this purpose hSOD1 transgenic mice (n=20) were treated with anle138b and compared with hSOD1 transgenic mice (n=20) which were given a placebo. By means of three experiments testing the motoric abilities of the mice (running wheel, grip strength and rotarod) as well as measurement of the weight of the mice, the beginning and the progress of the disease were observed. Additionally, survival of the mice was noted. 3. Findings Analysis of the data of the experiments and measurement of the weight showed that the treatment with anle138b did not influence the motoric abilities and the weight loss of the transgenic mice. There was neither a future beginning of the disease (115±14 days ) nor a longer survival (135±8 days) of the treated transgenic mice in comparison to the placebo treated transgenic mice (beginning of the disease 113±19 days, survival 133±10 days). 4. Conclusion The findings of this study suggest that the aggregation of SOD1 is not the crucial factor of the motor neuron degeneration in ALS because the protein aggregation inhibitor anle138b did not influence either the motoric abilities, the beginning and progress of the disease or the survival of the hSOD1-transgenic mice.	de
dc.contributor.coReferee	Wirths, Oliver PD Dr.
dc.subject.ger	Amyotrophe Lateralsklerose	de
dc.subject.ger	Neurodegenerative Erkrankung	de
dc.subject.ger	Motoneuron	de
dc.subject.ger	Familiäre ALS	de
dc.subject.ger	Sporadische ALS	de
dc.subject.ger	Superoxiddismutase 1	de
dc.subject.ger	Proteinaggregation	de
dc.subject.ger	hSOD1-Mausmodell	de
dc.subject.ger	Anle 138b	de
dc.subject.ger	Griffkraft	de
dc.subject.ger	Rotarod	de
dc.subject.ger	Laufrad	de
dc.subject.eng	Amyotrophic lateral sclerosis	de
dc.subject.eng	Neurodegenerative disease	de
dc.subject.eng	Motor neuron	de
dc.subject.eng	Familiar ALS	de
dc.subject.eng	Sporadic ALS	de
dc.subject.eng	Superoxiddismutase 1	de
dc.subject.eng	Protein aggregation	de
dc.subject.eng	hSOD1 mouse model	de
dc.subject.eng	Anle 138b	de
dc.subject.eng	Grip Strength	de
dc.subject.eng	Rotarod	de
dc.subject.eng	Running Wheel	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5EA3-0-4
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	GOK-MEDIZIN	de
dc.subject.gokfull	GOK-MEDIZIN	de
dc.description.embargoed	2014-07-01
dc.identifier.ppn	784906599

Files in this item

Name:DISSERTATION.pdf

Size:2.017Mb

Format:PDF

View/Open

Name:: DISSERTATION.pdf
Size:: 2.017Mb
Format:: PDF

View/Open

This item appears in the following Collection(s)

Human- und Zahnmedizin [3069]

Show simple item record