A novel pathway for transcriptional regulation of α-synuclein R. Lee Clough and Leonidas Stefanis 1 Division of Basic Neurosciences, Foundation for Biomedical Research of the Academy of Athens (IIBEAA), Athens, Greece 1 Correspondence: Division of Basic Neurosciences, Foundation for Biomedical Research of the Academy of Athens (IIBEAA), 11527 Athens, Greece. E-mail: lstefanis@bioacademy.gr α-Synuclein is an abundant neuronal protein that has been linked to both normal synaptic function and neurodegeneration—in particular, Parkinson’s disease (PD). Uncovering mechanisms that control α-synuclein transcription is therefore critical for PD pathogenesis and synaptic function. We previously reported that in PC12 cells and primary neurons, α-synuclein is transcriptionally up-regulated after application of growth factors. In the current work we have characterized the pathway involved in this regulation in PC12 cells. The MAP/ERK pathway, and in particular Ras, is both sufficient and necessary for the NGF and basic fibroblast growth factor (bFGF) -mediated response. Significantly, response elements for this pathway, including a putative occult promoter, lie within intron 1, a hitherto unappreciated regulatory region of the gene that may be utilized in this or other settings. The PI3 kinase pathway is also involved in α-synuclein regulation, but response elements for this pathway appear to lie primarily outside of intron 1. These findings indicate that NGF- and bFGF-mediated signal transduction via the MAP/ERK and PI3 kinase pathways, and in part via regulatory regions within intron 1, may be involved in α-synuclein transcriptional regulation. Targeting of these pathways may serve to modulate α-synuclein so that it achieves desirable levels within neuronal cells.—Clough, R. L., Stefanis, L. A novel pathway for transcriptional regulation of α-synuclein. Key Words: Parkinson’s disease • PC12 cells • ERK • PI3 kinase • NGF
End of preview. The entire article is 12 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/a-novel-pathway-for-transcriptional-regulation-of-synuclein-YyzIb0heUh
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
A novel pathway for transcriptional regulation of α-synuclein
Clough, R. Lee; Stefanis, Leonidas
Follow The FASEB Journal
, Volume 21 (2): 596
Fed of American Socs for Experimental Biology – Feb 1, 2007
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
