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

Josephine A Wright, Patrick C McHugh, Siyi Pan, Adam Cunningham, David R Brown

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalMolecular and Cellular Neurosciences
Volume57
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

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