miRNAs in protection and regeneration of dopaminergic midbrain neurons

by Anna-Elisa Roser
Doctoral thesis
Date of Examination:2016-04-12
Date of issue:2017-02-24
Advisor:Prof. Dr. Paul Lingor
Referee:Prof. Dr. Paul Lingor
Referee:Prof. Dr. André Fischer
Persistent Address: http://dx.doi.org/10.53846/goediss-6153

 

 

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Abstract

English

PD is the second most frequent neurodegenerative disorder affecting over 3 % of the population older than 80 years of age. Although PD is a system disorder which affects most regions of the brain, the progressive demise of the nigrostriatal projections and the inability of this system to regenerate are mainly responsible for the functional deficits observed. The etiology underlying PD is not finally resolved. Recent studies suggest that gene expression regulators might contribute to a large variety of disease states. miRNAs are small non-coding RNAs that are important for the post-transcriptional regulation of gene expression. Alterations in miRNA function have been reported in different neurodegenerative diseases including PD. Furthermore, miRNAs are auspicious therapeutic targets, as the manipulation of their expression might be neuroprotective or could induce the regeneration of neurons. In the present study the miRNAome of developing PMN cultures was analyzed and it was demonstrated that the major changes occur during early development. In order to analyze miRNA expression changes during degeneration and spontaneous regeneration of the murine nigrostriatal system a small RNA sequencing of the midbrain of the 6-OHDA mouse model for PD was performed and revealed novel sets of miRNAs involved in degeneration and regeneration of DA neurons in vivo. Taken together, miRNAs play an important role in development, maintenance and degeneration of DA neurons in vivo and in vitro and thus are promising targets for a better understanding of PD pathophysiology and the development of new therapeutic strategies.
Keywords: miRNA; dopaminergic neurons; neurodegeneration; Parkinson's disease; neuroregeneration; neuroprotection
 
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