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Comparison of microrna profiling of progressive supranuclear palsy in human brain tissues

2018
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Advisor: Doç. Dr. Bedia Palabıyık ; Prof. Dr. Mustafa Cengiz Yakıcıer

Abstract (EN)

Progressive Supranuclear Palsy (PSP) is a rare late onset disease that can be confused clinically with some other neurodegenerative diseases. Many cellular mechanisms are dysregulated and neuronal death is detected due to the aggregation of hyperphosphorylated tau proteins in the PSP affected brain tissue cells. The triggering mechanism underlying the pathological tau aggregation is not totally determined yet. However, some miRNAs (microRNAa) associated with the tau pathology have been reported in the literature. miRNAs, which are small regulatory molecules capable of effecting gene expressions of different cells and tissues as well as the cells they are produced in, have been associated with many diseases, are important in the study of pathological mechanisms, identification of marker and pharmacological targets. In this study, it was aimed to determine the expression levels of miRNAs that changed depending on pathogenesis of PSP. For the study, locus ceruleus autopsy brain sections' of the donors 'diagnosed with PSP' and healthy donors were provided by the 'Multiple Sclerosis and Parkinson's Tissue Bank'. Firstly, abnormal tau deposits were detected in the sections of the locus ceruleus autopsy brain tissues by using immunohistochemistry. Subsequently, changes in the levels of 800 miRNAs were examined in pathological regions showing immunoreactivity and not reactivity in PSP samples, and healthy donor controls. To detect the miRNA expression levels, The 'NanoString nCounter®' platform, which based on molecular barcoding approach can detect multiple targets sensitively, was used. As a result of the investigations, an overall decrease in expression levels of miRNAs was observed when the areas rich in tau pathology containing cells of PSP tissues were compared with the areas without tau pathology of PSP tissues and healthy control tissues. In this study, 24 miRNAs were detected that significantly and meaningful decreased in expression levels. Moreover, Of these miRNAs detected, it is thought that the 'hsa-miR-548 family with four members may be associated with tau pathology.

Author

Dr. Derya Özciğer Şenalp

How to Cite

Derya Özciğer Şenalp (Doctorate thesis). Comparison of microrna profiling of progressive supranuclear palsy in human brain tissues, 2018, İstanbul University.

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