Show simple item record

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

dc.contributor.advisorWeishaupt, Jochen Prof. Dr.
dc.contributor.authorThyssen, Stella
dc.titleEinfluss des Proteinaggregationshemmstoffs anle138b auf Beginn und Verlauf der Amyotrophen Lateralsklerose im transgenen hSOD1-Mausmodellde
dc.title.translatedInfluence of the protein aggregation inhibitor anle138b on the beginning and progression of amyotrophic lateral sclerosis in the transgenic hSOD1 mouse modelde
dc.contributor.refereeWeishaupt, Jochen Prof. Dr.
dc.description.abstracteng1. 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
dc.contributor.coRefereeWirths, Oliver PD Dr.
dc.subject.gerAmyotrophe Lateralsklerosede
dc.subject.gerNeurodegenerative Erkrankungde
dc.subject.gerFamiliäre ALSde
dc.subject.gerSporadische ALSde
dc.subject.gerSuperoxiddismutase 1de
dc.subject.gerAnle 138bde
dc.subject.engAmyotrophic lateral sclerosisde
dc.subject.engNeurodegenerative diseasede
dc.subject.engMotor neuronde
dc.subject.engFamiliar ALSde
dc.subject.engSporadic ALSde
dc.subject.engSuperoxiddismutase 1de
dc.subject.engProtein aggregationde
dc.subject.enghSOD1 mouse modelde
dc.subject.engAnle 138bde
dc.subject.engGrip Strengthde
dc.subject.engRunning Wheelde
dc.affiliation.instituteMedizinische Fakultätde

Files in this item


This item appears in the following Collection(s)

Show simple item record