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    题名: Octarepeat changes of prion protein in Parkinson's disease
    作者: Wang, Vinchi;Chuang, Tzu-chao;Soong, Bing-wen;Shan, Din-E.;Kao, Ming-ching
    贡献者: 淡江大學化學學系
    关键词: Polymorphism;Octarepeat;Nucleotide substitution;Copy deletion;Prion protein;Parkinson's disease
    日期: 2009-01-01
    上传时间: 2010-08-09 16:24:17 (UTC+8)
    出版者: London: Elsevier Ltd
    摘要: Polymorphism in prion protein (PrP) is related to different phenotypes of spongiform encephalopathies and some mental illnesses. The octarepeat region of PrP, encompassing the codon 51 through 91, is related to cellular anti-oxidation function and may play a role in genetic contribution of PrP polymorphism to neurodegeneration, such as Parkinson's disease (PD). We analyzed the genomic patterns of PrP gene from 528 subjects and found a predominance of Met/Met variant at codon 129 of PD subjects without significant difference (97.3%, and 96.5% in controls). But among PD subjects there were one with heterozygosity of silent nucleotide substitution (NS) on octarepeats (R1–2–3g–3–4/R1–2–2–3–4) and three with heterozygosity of single copy deletion (CD) on octarepeats (R1–2–3–4/R1–2–2–3–4). Consistent genomic DNA and cDNA sequences were found in a PD subject without any octarepeat changes and the one with NS, but R1–2–3g–3–4/R1–2–2–3–4 of cDNA pattern occurred in the one with genomic CD. This is the first report of the polymorphic PrP octarepeat change among those with parkinsonism. We proposed a hypothesis about an initial secondary hairpin structure of the template strand followed by the transcript “shift backward” due to the high homology of the sequences between R2 and R3 motifs while synthesizing RNA. This phenomenon may be a key step of neurodegeneration resulting from PrP polymorphism and require further studies.
    關聯: Parkinsonism & Related Disorders 15(1), pp.53-58
    DOI: 10.1016/j.parkreldis.2008.03.003
    显示于类别:[化學學系暨研究所] 期刊論文

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