Molecular Genetics of Neuronal Disorders caused by amyloid deposition.

淀粉样蛋白沉积引起的神经元疾病的分子遗传学。

• 批准号: 01480157
• 负责人: SAKAKI Yoshiyuki
• 金额: $ 4.03万
• 依托单位: Institute of Medical Science, The University of Tokyo (1991)Kyushu University (1989-1990)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480157/
• 关键词: Alzheimer's disease; Neuron; Genetic Disease; Familial Amyloidosis; Transthyretin; beta amyloid; Aging; 家族性アミロイド-シス; 脳; 痴呆; 遺伝子; アミロイド; 神経難病; アミロイド-シス; ベ-タたん白; 遺伝子工学

We investigated the molecular basis of neurodegenerative disorders including familial amyloidotic polyneuropathy (FAP) and Alzheimer's disease (AD). Major conclusion we obtained are :(1) We colned the entire region of the amyloid protein precursor gene and determined the nucleotide sequences of all the exons and their flanking regions.(2) Screening of familial Alzheimer's disease (FAD) families in Japan led us to identified a FAD family carrying a mutation at position 717 of the APP gene.(3) Haplotypes of FAP families in Japan were determined, which strongly suggested that Met-30 FAP is multiple origin.(4) An E. coli production system of the variant transthyretin (TTR) was established, which allowed us to prepare any types of TTR was purified, crystalized and now subjected to x-ray crystallographic studay.(5) Several new mutations related to hereditary Creutzfeldt-Jacob disease were found in the prion gene.

我们研究了神经退行性疾病的分子基础，包括家族性淀粉样变性多神经病变（FAP）和阿尔茨海默病（AD）。得到的主要结论有：(1)克隆了淀粉样蛋白前体基因的整个区域，并确定了所有外显子及其侧翼区的核苷酸序列。(2)通过对日本家族性阿尔茨海默病（FAD）家族的筛查，我们发现了一个携带APP基因717位突变的FAD家族。(3)测定了日本FAP家族的单倍型，强烈提示Met-30 FAP具有多源性。(4)建立了变异体转甲状腺素（TTR）的大肠杆菌生产体系，使我们能够制备任何类型的TTR，并对其进行纯化、结晶和x射线晶体学研究。(5)在遗传克雅氏病相关的朊病毒基因中发现了几个新的突变。

项目成果

Sakaki,Y: "Human transthyretin (prealbumin) gene and molecular genetics of amyloidotic polyneuropathy" Mol.Biol.Med.6. 161-168 (1989)

Sakaki，Y：“人类转甲状腺素蛋白（前白蛋白）基因和淀粉样多发性神经病的分子遗传学”Mol.Biol.Med.6。

Yamada,T.: "Expression of Alzheimer Amyloid betaーprotein precursor gene in neuronal cells" Gerontology. 37. 24-30 (1991)

Yamada, T.：“阿尔茨海默病淀粉样β蛋白前体基因在神经元细胞中的表达”《老年学》37. 24-30 (1991)。

K.Dohーura,: "CreutzfeldtーJakob disease Patients with Congophili kuru Plaques Have the Missense Variant Prion Protein Common to GerstmannーSta^^‥ussler Syndorome." Annals.of Neurology. 27. 121-126 (1990)

K. Dohura，：“患有刚果库鲁斑块的克雅氏病患者具有 Gerstmann-Sta^^‥ussler 综合征常见的错义变异朊病毒蛋白”，《神经病学年鉴》27。121-126。

Yoshioka,K.: "The ^<717>Val→Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups." B.B.R.C.178. 1141-1146 (1991)

Yoshioka, K.：“淀粉样前体蛋白中的 ^<717>Val→Ile 取代与家族性阿尔茨海默病相关，无论种族如何。”B.B.R.C.178 (1991)。

Y.Sakaki,: "Genetic analysis of familial amyloidtic polyneuropathy,an automosomal dominant disease." Clinica.Chinica.Acta.185. 291-298 (1989)

Y.Sakaki：“家族性淀粉样多发性神经病的基因分析，一种常染色体显性遗传病。”