التفاصيل البيبلوغرافية
| العنوان: |
Regulation of sorLA in general and in Alzheimer's disease |
| المؤلفون: |
Andersen, Olav Michael, Poulsen, Annemarie Svane Aavild, Zole, Egija, Ivarsen, Anne Kathrine, Blechingberg, Jenny, Vorum, Henrik |
| المصدر: |
Andersen , O M , Poulsen , A S A , Zole , E , Ivarsen , A K , Blechingberg , J & Vorum , H 2014 , ' Regulation of sorLA in general and in Alzheimer's disease ' , Alzheimer`s Association International Conference , Copenhagen , Denmark , 13/07/2014 - 17/07/2014 . |
| سنة النشر: |
2014 |
| المجموعة: |
Aarhus University: Research |
| مصطلحات موضوعية: |
functional assay,molecular biology |
| الوصف: |
Background: The Sortillin-related receptor (sorLA) is involved in cellular trafficking and processing of the Amyloid precursor protein (APP). A decrease in sorLA expression has been identified in brain tissue from patients suffering from Alzheimer's disease (AD), suggesting that sorLA may be a key regulator of Aß production and that sorLA activity protects against AD. Furthermore, association between Single Nucleotide Polymorphisms (SNPs) from the gene encoding sorLA (gene name: SORL1) and AD was recently identified; suggesting that transcription of SORL1 could be linked to the development of AD. The mechanism behind the regulation of SORL1 expression in general and how AD-associated SNPs influence sorLA levels during AD, has not yet been characterized. Methods: To identify cis - and trans -regulatory factors important for the expression of sorLA, we studied the proximal promoter of SORL1 using in silico analysis and generated promoter constructs for Dual Luciferase Assay. We precipitated proteins from nuclear cell extracts binding to the SORL1 promoter using Streptavidin magnetic beads and biotinylated oligomers. By introduction of constructs for over expression and siRNA molecules for under expression of transcription factors, we determined their effects on sorLA expression by qPCR and Western blotting. Using site-directed mutagenesis we mapped regulatory cis-element binding sites for verified transcription factors. Results: We have identified regions in the SORL1 promoter, important for induction as well as repression of sorLA expression. We identified several trans cription factors that is directly involved in the regulation of sorLA expression, and mapped their binding sites within the proximal SORL1 promoter. Finally, we determined the level of these transcription factors in brain tissue from patients with Alzheimer's disease. Conclusions: We have investigated the regulation of sorLA expression and identified several cis - and trans -regulatory elements important for the proper expression of sorLA. These ... |
| نوع الوثيقة: |
conference object |
| اللغة: |
English |
| الاتاحة: |
https://pure.au.dk/portal/da/publications/regulation-of-sorla-in-general-and-in-alzheimers-disease(20fb9e47-1cfc-4d33-a80f-2f5712d67d91).html |
| Rights: |
info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: |
edsbas.4DDBE97E |
| قاعدة البيانات: |
BASE |