Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level.
Alpha-synuclein is a cytosolic protein associated with a range of diseases including Parkinson's disease. In these diseases alpha-synuclein aggregates and this is believed to play a causative role in disease progression. Alpha-synuclein aggregation has been suggested to be caused by increased expression levels and has also been suggested to be countered by increased beta-synuclein expression. In this regard, strategies to counter-regulate the expression of the synucleins by increasing beta-synuclein expression relative to alpha-synuclein may be beneficial in preventing disease progression. We therefore studied the regulation of alpha-synuclein to try to identify pathways that might counter-regulate the synucleins. We identified members of the ZSCAN family of transcription factors as specific repressors of alpha-synuclein. In particular ZSCAN21 was found to both repress alpha-synuclein and increase beta-synuclein expression. These findings support the notion that a single pathway in the cell can counter-regulate the expression of the synucleins. Support for this came from experiments that showed that ZSCAN21 expression decreases alpha-synuclein aggregation in the cells.
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Josephine A
JA
Wright
Patrick C
PC
McHugh
Siyi
S
Pan
Adam
A
Cunningham
David R
DR
Brown
D045744:Cell Line, Tumor; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*; D051846:beta-Synuclein / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D014157:Transcription Factors; D051844:alpha-Synuclein; D051846:beta-Synuclein
NRF2; Parkinson's disease; Synuclein; Transcription factors; ZSCAN