Biochemical analysis of abnormal prion protein in the cases with sporadic Creutzfeldt-Jakob disease.

散发性克雅氏病病例中异常朊病毒蛋白的生化分析。

• 批准号: 17500232
• 负责人: SASAKI Kensuke
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500232/
• 关键词: prion disease; prion protein types; immunoblot; oligomer; Creutzfeldt-Jakob disease; 凝集体; 遠心カラム; 孤発性ヤコブ病; プリオン蛋白; 電気泳動

We could examine one case with sporadic Creutzfeldt-Jakob disease (CJD) in Japan that expressed co-occurrence of type 1 and type 2 protease-resistant prion protein (PrP). Pathological features of the unique case showed both synaptic and perivacuolar PrP depositions. Coexistence of type 1 and type 2 PrP was observed in only single case (4.5%) among 22 cases examined. We have examined PrP types in sporadic CJD cases in United Kingdom and found that 7 (38.9%) out of 18 cases showed coexistence of type 1 and type 2 PrP, which was significantly higher level than in Japan. Genetic differences among races were also elucidated as reported previously ; codon 129 polymorphism of the prion protein gene consisted entirely of methionin homozygosity in all Japanese cases (100%), in contrast with UK cases (55.6%). Although the pathological grade of pontine nuclei varied among cases, the severity was not affected by the difference of pathogen strain, but merely by the time course of disease progression. Homogeneity of PrP types and clinicopathological features in Japanese sporadic CJD cases may be based on the ethnic background in part.Because the biochemical properties of protease-resistant PrP in Japanese sporadic CJD cases were relatively homogeneous, we tried to detect PrP oligomers so that we could classify the abnormal PrP based on the conformational differences. We determined an alternative method, which would be a simple and riskless procedure to detect PrP aggregates. The optimized condition was established to solubilize cellular PrP as monomers and leave abnormal PrP as aggregates or oligomers. Therefore we could separate PrP aggregates by the simple method in a shorter time. Recently it has been found that PrP oligomers rather than highly aggregated PrP fibrils have more potent infectivity and neurotoxicity. This simple method for PrP oligomer detection may be suitable for practical use for the analysis of prion diseases.

我们可以检查一例散发性克雅氏病（CJD）在日本，表达1型和2型蛋白酶抗性朊蛋白（PrP）的共同出现。病理特征的独特情况下，突触和泡周PrP沉积。在22例受检者中，仅1例（4.5%）同时存在1型和2型PrP。我们在英国的散发性CJD病例中检测了PrP类型，发现18例病例中有7例（38.9%）显示1型和2型PrP共存，这一水平明显高于日本。种族间的遗传差异也阐明了以前的报告，密码子129多态性的朊病毒蛋白基因完全由甲硫氨酸纯合性在所有日本的情况下（100%），与英国的情况下（55.6%）。虽然脑桥核的病理分级在病例之间存在差异，但其严重程度不受病原体菌株差异的影响，而仅受疾病进展的时间过程的影响。日本散发性CJD病例中PrP类型和临床病理特征的同质性可能部分基于种族背景，因为日本散发性CJD病例中蛋白酶抗性PrP的生化特性相对同质，我们试图检测PrP寡聚体，以便我们可以根据构象差异对异常PrP进行分类。我们确定了一种替代方法，这将是一个简单和无风险的程序来检测PrP聚集体。建立了最佳条件，以溶解细胞PrP作为单体，并留下异常PrP作为聚集体或寡聚体。因此，我们可以用简单的方法在较短的时间内分离PrP聚集体。最近发现PrP寡聚体比高度聚集的PrP原纤维具有更强的感染性和神经毒性。这种简单的PrP寡聚体检测方法可能适用于朊病毒疾病的分析。

项目成果

Clusterin expression in follicular dendritic cells associated with prion protein accumulation

• DOI: 10.1002/path.2009
• 发表时间: 2006-08-01
• 期刊: JOURNAL OF PATHOLOGY
• 影响因子: 7.3
• 作者: Sasaki, K.;Doh-ura, K.;Iwaki, T.
• 通讯作者: Iwaki, T.

CJDの病理学的評価基準

克雅氏病病理学评估标准

• 发表时间: 2006
• 期刊: CLINICAL NEUROSCIENCE 24
• 作者: Toyoshima Y;Onodera O;Yamada M;Tsuji S;Kozak JA;Kozak JA;Matsushita M;Michiue H;Matsushita M;Wu HY;Michiue H;Matsushita M;Wu HY;Michiue H;Noguchi H;Wu HY;Matsushita M;Arataki S;Michiue H;Fujimi K;Fujimi K;Fujimi K;Sasaki K;Noda K;Ishikawa K;Kawatake S;佐々木健介;Sasaki K;Ishikawa K;Kawatake S;佐々木健介
• 通讯作者: 佐々木健介

Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle‐only dementia): The Hisayama study

• DOI: 10.1111/j.1440-1789.2006.00722.x
• 发表时间: 2006-12
• 期刊: Neuropathology
• 影响因子: 2.3
• 作者: K. Noda;K. Sasaki;Kohei Fujimi;Y. Wakisaka;Yumihiro Tanizaki;Y. Wakugawa;Y. Kiyohara;M. Iida;H. Aizawa;T. Iwaki

Fatal familial insomnia with an unusual prion protein deposition pattern: an autopsy report with an experimental transmission study

• DOI: 10.1111/j.1365-2990.2004.00592.x
• 发表时间: 2005-02-01
• 期刊: NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
• 影响因子: 5
• 作者: Sasaki, K;Doh-ura, K;Iwaki, T
• 通讯作者: Iwaki, T

Altered expression of COX-2 in subdivisions of the hippocampus during aging and in Alzheimer's disease: The Hisayama study

• DOI: 10.1159/000101957
• 发表时间: 2007-01-01
• 期刊: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
• 影响因子: 2.4
• 作者: Fujimi, Kouhei;Noda, Kazuhito;Iwaki, Toru
• 通讯作者: Iwaki, Toru