Neuronal death in Alzheimer's disease.
Neuronal death in Alzheimer's disease.
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阿尔茨海默病中的神经元死亡。
DOI：
10.2169/internalmedicine.39.328
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发表时间：
2000
影响因子：
1.2
通讯作者：
K. Yanagisawa
中科院分区：
文献类型：
--
作者：
K. Yanagisawa
仅由一种蛋白质的缺陷引起。然而，尽管进行了许多细胞遗传学和生物学研究，WShas 的主要缺陷仍然难以捉摸。因此，我们于 1989 年启动了一项研究项目，以分离导致 WS(WRN) 的基因。在纯合性分析、扩展纯合性分析、连锁不平衡研究和单倍型研究的基础上，构建了8号染色体短臂的遗传、物理和表达图谱，缩小了WRN位点的位置。经过我们的努力，我们于 1996 年鉴定出了 WRN 基因 (2)。 WRN基因是5.2kb全长cDNA克隆，其编码1,432个氨基酸的预测蛋白质。 WRN 序列与已知蛋白质的比较表明与 DNA 和 RNA 解旋酶超家族中的基因具有惊人的同源性。这些基因包括 RECQ1（人）、F1 8C5C（秀丽隐杆线虫）、SgSI（酿酒酵母）和 RecQ（大肠杆菌）。共享同源区域位于蛋白质 (WRN-H) 的中心，从氨基酸 540 到 963（解旋酶结构域）。除了解旋酶结构域外，WRN 氨基酸序列与已知基因没有任何显着的同源性。因此，WS 加入了由解旋酶基因突变引起的遗传性疾病名单中。这些疾病是着色性干皮病、并发症 B 组和 D 组（分别是解旋酶 ERCC2 和 ERCC3）、毛发硫营养不良症 (ERCC2)、Cockayne 综合征（解旋酶 ERCC6）、BS 和 X 染色体连锁地中海贫血智力低下综合征（表 3）。这五个解旋酶分为两组。一组（XPB、XPD和CSB）与其他蛋白质结合，并由蛋白质复合物、转录因子II H组成。另一组（WRN和BLM）未检测到它们的结合蛋白。 WS和BS具有相同的同源酵母Sgsl基因，但两种综合征的表型略有差异。为了澄清这些差异，需要进一步研究。
be caused by defects of only one protein. However, despite many cytogenetic and biological studies, the primary defect in WShas remained elusive. In 1989, we therefore started a research project to isolate the gene responsible for WS(WRN). Wehave constructed a genetic, physical and expression map in the short arm of chromosome8 and narrowed the position of the WRNlocus on the basis of a homozygosity analysis, an extended homozygosity analysis, a linkage disequilibrium study and a haplotype study. As a result of our endeavor, in 1996, we identified the WRNgene (2). The WRNgene is a 5.2 kb full-length CDNAclone which encodes a predicted protein of 1 ,432 amino acids. Comparison of the WRNsequences to knownprotein shows a striking homology to genes in the superfamily of DNAand RNAhelicases. These genes include RECQ1(man), F1 8C5C (Caenorhabditis elegans), SgSI (Saccharomyces cerevisiae) and RecQ (Escherichia coli). The region of shared homology is in the center of the protein (WRN-H), spanning from amino acid 540 to 963, the helicase domain. Other than the helicase domain, the WRN amino acid sequence does not show any significant homology to known genes. Thus, WSjoins a list of inherited disorders caused by mutations in helicase genes. These disorders are xeroderma pigmentosum, complication group B and D (helicase ERCC2and ERCC3, respectively), trichothiodystrophy (ERCC2), Cockayne syndrome (helicase ERCC6), BS and X chromosome-linkeda-thalassemia mental retardation syndrome (Table 3). These five helicases are divided to two groups. One group, XPB, XPDand CSB, bind other proteins and consist of protein complex, transcription factor II H. In the case of another group, WRNand BLM,their binding proteins were not detected. WSand BS shared the same homologous yeast Sgsl gene, however there are slightl differences in phenotype between the two syndromes. To clarify these differences, further study is needed.
影响因子：
56.9
作者：
SUZUKI, N;CHEUNG, TT;YOUNKIN, SG
通讯作者：
YOUNKIN, SG
影响因子：
56.9
作者：
CAI, XD;GOLDE, TE;YOUNKIN, SG
通讯作者：
YOUNKIN, SG