第二及十七型脊髓小腦共濟失調症之分子檢測及SCA17 TBP擴增淋巴細胞的氧化壓力研究

Genetic testing of spinocerebellar ataxia types 2 and 17 and oxidative stress study of lymphoblastoid cells with SCA17 TBP expansion

陳玢璘(FL Chen)

指導教授 ： 李桂楨

國立臺灣師範大學/理學院/生命科學研究所/碩士(2005年)

摘要

無資料

關鍵字

氧化壓力 ； 神經退化疾病 ； 小腦萎縮症 ； 淋巴細胞 ； 脊髓小腦共濟失調症

並列摘要

Abstract

Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders characterized by cerebellar dysfunction alone or in combination with other neurological abnormalities. Among them, both SCA2 and SCA17 were caused by the expansions of coded CAG trinucleotide repeats. The chromosome 6q27 SCA17 gene encodes a transcription initiation factor TATA-box binding protein (TBP). In this study, SCA2 and SCA17 genotyping was performed to set up the repeat size range in Taiwanese control subjects and in patients with ataxia, dementia, PD, schizophrenia, and other neurological disorders. For SCA2, one borderline (32 repeats) and four pathogenic (35, 40, 48, and 49 repeats) alleles were observed in patients group. For SCA17, no pathogenic expansion was found, but five borderline alleles (44~46 repeats) were found in patients group. To investigate the pathogenic mechanisms underlying the disease, EBV-transformed lymphoblastoid cells from controls and patients with SCA17 TBP expansions were established. Constructs with 3~61 CAG repeat-containing TBP cDNA were also prepared and expressed in SK-N-SK cells to assess the oxidative tolerance of cells upon exposure to t-butylhydroperoxide (TBH). By quantifying the cell viability and the amount of SOD upon TBH treatment, the cells expressed expanded TBP were shown to be more vulnerable to TBH than the cells expressed normal TBP. Quantitative proteomics was used to compare the overall protein expressions among lymphoblastoid cells from SCA17 patients and normal controls. So far, some heat shock factors and oxidative stress related proteins have been suggested from the peer results.

並列關鍵字

Oxidative Stress ； SCA17 ； spinocerebellar ataxia ； neurodegeneration ； lymphoblastoid ； CAG ； TBP