کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6282092 | 1615133 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Novel and functional ABCB1 gene variant in sporadic Parkinson's disease
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کلمات کلیدی
ABCB1UCHL-1Leucine-rich repeat kinase 1LRRK1PTEN-induced kinase 1ATP-binding cassette sub-family B member 1DNA sequence variantsDSVsATP13A2SNCAGBADJ-1PINK1FOXO3aFOXO1SNPsSp1 - SP1Sp3 - sp3Parkinson’s disease - بیماری پارکینسونBlood–brain barrier - سد خونی مغزیBBB - سد خونی مغزیSpecificity protein 1 - مشخصات پروتئین 1Promoter - پروموتر
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Parkinson's disease (PD) is a common progressive neurodegenerative disease. Most cases of PD are sporadic, which is caused by interaction of genetic and environmental factors. To date, genetic causes for sporadic PD remain largely unknown. ATP-binding cassette sub-family B member 1 (ABCB1) is a membrane-associated protein that acts as an efflux transporter for many substrates, including chemotherapeutic agents, anti-epilepsy medicine, antibiotics and drugs for PD. ABCB1 gene is widely expressed in human tissues, including endothelial cells of capillary blood vessels at blood-brain barrier sites. In PD patients, decreased ABCB1 levels have been reported. We speculated that misregulation of ABCB1 gene expression, caused by DNA sequence variants (DSVs) within its regulatory regions, may be involved in PD development. In this study, we genetically and functionally analyzed the proximal promoter of the human ABCB1 gene, which is required for constitutive expression, in sporadic PD patients and healthy controls. The results showed that a novel and heterozygous DSV g.117077G>A was identified in one PD patient, but in none of the controls. This DSV significantly altered the transcriptional activity of the ABCB1 gene promoter in transiently transfected HEK-293 cells. A heterozygous DSV g.116347T>C was only found in one control. Four single-nucleotide polymorphisms, g.116154T>C (rs28746504), g.117130A>G (rs2188524), g.117356C>G (rs34976462) and g.117372T>C (rs3213619), and one heterozygous deletion DSV g.116039del were found in PD patients and controls with similar frequencies. Therefore, our findings suggest that ABCB1 gene promoter DSVs may contribute to PD development as a rare risk factor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 566, 30 April 2014, Pages 61-66
Journal: Neuroscience Letters - Volume 566, 30 April 2014, Pages 61-66
نویسندگان
Yuequn Li, Yonghua Li, Shuchao Pang, Wenhui Huang, Aimei Zhang, Robert G. Hawley, Bo Yan,