• Deutsch
    • English
  • English 
    • Deutsch
    • English
  • Login
Item View 
  •   Home
  • Medizin
  • Human- und Zahnmedizin
  • Item View
  •   Home
  • Medizin
  • Human- und Zahnmedizin
  • Item View
JavaScript is disabled for your browser. Some features of this site may not work without it.

Analyse des PPAR-a-Liganden Fenofibrat auf die ABCD1-defiziente Maus

Analysis of the effects of PPAR-a-ligand fenofibrate on ABCD1-deficient mice

by Johannes Linßen
Doctoral thesis
Date of Examination:2014-07-14
Date of issue:2014-07-08
Advisor:Prof. Dr. Michael Werner Sereda
Referee:Prof. Dr. Michael Werner Sereda
Referee:PD Dr. Sven Thoms
crossref-logoPersistent Address: http://dx.doi.org/10.53846/goediss-4580

 

 

Files in this item

Name:Johannes_Linßen_MDthesis.pdf
Size:1.74Mb
Format:PDF
ViewOpen

The following license files are associated with this item:


Abstract

English

The X-linked adrenoleukodystrophy is a peroxisomal hereditary metabolic disease that is due to the loss of function of the peroxisomal transmembrane transporter ABCD1. We distinguish between the frequent progressive forms of infantile cerebral adrenoleukodystrophy (CALD) and the adrenomyeloneuropathy (AMN). While the AMN usually only manifests between the twentieth and thirtieth year, the CALD already in the first years of life occurs and lethal disease. Due to loss of function of the transmembrane transporter it comes to the accumulation of very long chain fatty acids and to an inflammatory demyelination in the nervous system. Mice in which the gene has been switched off ABCD1, only show a AMN-like phenotype, mice with complete loss of function of peroxisomes in myelinating cells, however, an inflammatory demyelination. It is therefore assumed as a result of ABCD1 deficiency as the cause of cerebral degeneration is a secondary, extensive loss of function of peroxisomes. In the present work, ABCD1-/ - mice treated for 30 days with 3 different concentrations of the PPARa agonist fenofibrate. The aim was to investigate the tolerability of the drug in a long-term study and the effects of fenofibrate on peroxisomal proteins in the brain. It was found that the expression of peroxisomal membrane proteins, enzymes of the peroxisomal β-oxidation, as well as anti-oxidative enzymes peroxisomal in the mouse brain can be modulated by treatment with fenofibrate. It was noticeable that the lowest administered dose of the drug often the concentration of the investigated proteins lowered, a higher concentration, however, had the opposite effect. In addition, the substance has been found in the treatment period of 30 days either on the basis of motor tests, nor by weight loss for mice as toxic. Whether the effects on the direct effects of fenofibrate, or indirectly by messengers due from peripheral tissues, have not been studied. The results presented give reason to investigate the effect of fenofibrate with regard to the treatment of leukodystrophies on.
Keywords: fenofibrate; x-linked adrenoleukodystrophy; PPAR; Abcd1
Schlagwörter: Adrenoleukodystrophie; Abcd1; PPAR; Fenofibrat
 

Statistik

Publish here

Browse

All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesType

Help & Info

Publishing on eDissPDF GuideTerms of ContractFAQ

Contact Us | Impressum | Cookie Consents | Data Protection Information
eDiss Office - SUB Göttingen (Central Library)
Platz der Göttinger Sieben 1
Mo - Fr 10:00 – 12:00 h


Tel.: +49 (0)551 39-27809 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
ediss_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]
Göttingen State and University Library | Göttingen University
Medicine Library (Doctoral candidates of medicine only)
Robert-Koch-Str. 40
Mon – Fri 8:00 – 24:00 h
Sat - Sun 8:00 – 22:00 h
Holidays 10:00 – 20:00 h
Tel.: +49 551 39-8395 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
bbmed_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]