Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level

Wright, Josephine A., McHugh, Patrick C., Pan, Siyi, Cunningham, Adam and Brown, David R. 2013. Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level. Molecular and Cellular Neuroscience 57 , pp. 33-41. 10.1016/j.mcn.2013.09.002

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Synuclein; Parkinson's disease; Transcription factors; ZSCAN; NRF2
Publisher:	Elsevier
ISSN:	1044-7431
Last Modified:	19 Oct 2021 01:25
URI:	https://orca.cardiff.ac.uk/id/eprint/87905

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