Molecular effects of protein alpha synuclein in the nucleus: DNA binding and transcriptional regulation

Gotovac, Kristina (2014) Molecular effects of protein alpha synuclein in the nucleus: DNA binding and transcriptional regulation. Doctoral thesis, Faculty of Science > Department of Biology.

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Protein alpha synuclein is involved in vesicular transport on synapses and regulation of dopamine release. There is the evidence that alpha-synuclein may play an important role in in Parkinson`s disease (PD) development but the mechanism by which alpha synuclein damages dopaminergic neurons remains elusive. As alpha synuclein is located in the nucleus of neurons and it has been shown that it binds DNA, one of the possible mechanisms is transcriptional dysregulation. The aim of the project was to investigate possible effects of alpha-synuclein in the nucleus as well as possible mechanisms of transcriptional deregulation in PD models. Gene ontology analysis and pathways analysis showed that genes recruited by endogenous alpha synuclein are mostly involved in synapse functioning and organization, development of central nervous system and ubiquitin proteasome system. In cells overexpressing alpha synuclein most of the genes were related to nucleus and transcriptional regulation, while in cells transfected with mutated alpha synuclein (A53T) recruited genes were mostly involved in apoptosis regulation and pathways involved in development of genetic and neurologic diseases. Experiments showed significant influence of endogenous and mutated alpha synuclein on promoters of genes NEDD4 (ubiquitin-ligase), SLC4A5 (sodium bicarbonate cotransporter), NRXN3 (receptor and cell adhesion molecule), ADRA1A (adrenergic receptor) and MAP4K4 (mitogen activated protein kinase). Overall results show potential effect of alpha synuclein in the nucleus, primarily through effect on transcriptional mechanisms that can finally lead to Parkinson`s disease development.

Item Type: Thesis (Doctoral thesis)
Keywords: alpha synuclein, transcriptional regulation, Parkinson`s disease, chromatin immunoprecipitation, gene ontology
Supervisor: Borovečki, Fran
Date: 2014
Number of Pages: 123
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 19 Jan 2015 12:05
Last Modified: 19 Jan 2015 12:05

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