Effects of the microRNA cluster 132/212 in primary dopaminergic neurons

by Jonas Sebastian Schünemann
Doctoral thesis
Date of Examination:2021-03-18
Date of issue:2021-02-19
Advisor:Prof. Dr. Paul Lingor
Referee:Prof. Dr. Paul Lingor
Referee:Prof. Dr. Tiago Fleming Outeiro
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-8429

 

 

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Abstract

English

The microRNA (miRNA) cluster 132/212 is highly involved in the regulation of cell growth and maturation in neurons and other cell types. This work investigated effects of increased levels of the miRNA strands miR-132-3p and miR-212-3p in primary dopaminergic neurons (PMN). Cells transfected with miR-132-3p showed enhanced neurite growth and improved regeneration after mechanical lesion in primary dopaminergic neurons but had an unchanged survival in a cell stress model. Elevated levels of miR-212-3p did not alter the experimental read-outs. In a mass spectrometry approach alteration of the PMN proteome after transfection with the respective protein strands were investigated. ARHGAP32 and MECP were confirmed as targets of miR-132-3p and EPHA5 as a target of miR-212-3p by Western blot. By regulating the expression of the described proteins, the observed effects of elevated miR-132-3p levels on cell growth and regeneration can partly be explained. The underlying mechanism could be an interesting approach for possible therapeutic use in neurodegenerative disease like Parkinson's disease.
Keywords: miR-132/212 cluster; miR-132; miR-212; primary dopaminergic neurons
 
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