Transcriptional regulation of the α-synuclein gene in human brain tissue.

Abstract:

:The transcriptional regulation of the gene encoding α-synuclein (SNCA) is thought to play a critical role in the pathogenesis of Parkinson's disease (PD), as common genetic variability in this gene is associated with an elevated risk of developing PD. However, the relevant mechanisms are still poorly understood. So far, only few proteins have been identified as transcription factors (TFs) of SNCA in cellular models. Here we show that two of these TFs bind to the DNA in human brain tissue: the zinc finger protein ZSCAN21 occupies a region within SNCA intron 1, as described before, while GATA2 occupies a specific region within intron 2, where we have identified a new binding site within the complex structure of the 5'-promoter region of SNCA. Electrophoretic mobility shift assays confirmed these binding sites. Genetic investigations revealed no polymorphisms or mutations within these sites. A better understanding of TF-DNA interactions within SNCA may allow to develop novel therapies designed to reduce α-synuclein levels.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Brenner S,Wersinger C,Gasser T

doi

10.1016/j.neulet.2015.05.029

subject

Has Abstract

pub_date

2015-07-10 00:00:00

pages

140-5

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(15)00386-9

journal_volume

599

pub_type

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