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The protein alpha-synuclein whose expression is strongly implicated in Parkinson's disease (PD) is not only expressed in the central nervous system (CNS) but also in the enteric nervous system (ENS). The growing body of evidence suggesting that gastrointestinal inflammation is involved in the development of PD led us to investigate the effects of inflammation on alpha-synuclein expression in primary culture of rat ENS and in mice with dextran sulfate sodium (DSS)-induced colitis. Using western blot and qPCR, we found that both LPS and a combination of TNF-α and IL1-β (TNF-α/IL1-β) decreased the expression levels of alpha-synuclein in primary culture of rat ENS, an effect that was prevented in the presence of the p38 inhibitors SB203580 and BIRB 796. LPS and TNF-α/IL1-β had no effect on alpha-synuclein expression in primary culture of rat CNS and in HEL cells. In mice, acute but not chronic DSS-induced colitis was associated with a decreased expression of colonic alpha-synuclein. As a whole, our findings indicate that acute inflammatory insults downregulate alpha-synuclein expression in the ENS via a p38 pathway. They provide new insights into the widely discussed concepts of alpha-synuclein expression and aggregation in the ENS in PD and raise issues about the possible role of gastrointestinal inflammation in the development of PD. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Journal of neurochemistry
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A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.
A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.
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