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 journalArticle

14 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.

LanguageEnglish
Pages33-41
Number of pages9
JournalMolecular and Cellular Neurosciences
Volume57
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Fingerprint

beta-Synuclein
alpha-Synuclein
Synucleins
Disease Progression
Cell Aggregation
Parkinson Disease
Transcription Factors

Cite this

Wright, Josephine A ; McHugh, Patrick C ; Pan, Siyi ; Cunningham, Adam ; Brown, David R. / Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level. In: Molecular and Cellular Neurosciences. 2013 ; Vol. 57. pp. 33-41.
@article{c504fa9527f74842b95d025d9517be1e,
title = "Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level",
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.",
keywords = "Cell Line, Tumor, Humans, RNA, Messenger/genetics, Transcription Factors/genetics, Transcriptional Activation, alpha-Synuclein/genetics, beta-Synuclein/genetics",
author = "Wright, {Josephine A} and McHugh, {Patrick C} and Siyi Pan and Adam Cunningham and Brown, {David R}",
note = "{\circledC} 2013.",
year = "2013",
month = "11",
doi = "10.1016/j.mcn.2013.09.002",
language = "English",
volume = "57",
pages = "33--41",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",

}

Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level. / Wright, Josephine A; McHugh, Patrick C; Pan, Siyi; Cunningham, Adam; Brown, David R.

In: Molecular and Cellular Neurosciences, Vol. 57, 11.2013, p. 33-41.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level

AU - Wright, Josephine A

AU - McHugh, Patrick C

AU - Pan, Siyi

AU - Cunningham, Adam

AU - Brown, David R

N1 - © 2013.

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

KW - Cell Line, Tumor

KW - Humans

KW - RNA, Messenger/genetics

KW - Transcription Factors/genetics

KW - Transcriptional Activation

KW - alpha-Synuclein/genetics

KW - beta-Synuclein/genetics

U2 - 10.1016/j.mcn.2013.09.002

DO - 10.1016/j.mcn.2013.09.002

M3 - Article

VL - 57

SP - 33

EP - 41

JO - Molecular and Cellular Neurosciences

T2 - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

SN - 1044-7431

ER -