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 Lettjournal_title
Neuroscience lettersauthors
Brenner S,Wersinger C,Gasser Tdoi
10.1016/j.neulet.2015.05.029subject
Has Abstractpub_date
2015-07-10 00:00:00pages
140-5eissn
0304-3940issn
1872-7972pii
S0304-3940(15)00386-9journal_volume
599pub_type
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