2017-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/679869摘要:金屬硫蛋白的分子特性和構造: 金屬硫蛋白為一類小分子量的蛋白,其分子量約為 6000~14000 Da。其共61-68個氨基酸中,cysteine (半胱氨酸)即佔20個,通常以Cys-X-Cys的序列存在。因為為一種富含 (30%) 半胱氨酸 (cysteine)的蛋白質:其硫醇 (thiol group) 官能機。這樣的結構發現可以結合鎘金屬的蛋白質導致金屬硫蛋白, metallothioneins (MTs),。可以除了與鎘結合以外,鋅,銅等重金屬也可以與MTs結合。因此可以調節體內金屬的平衡以及防止重金屬的中毒的功能等。目前為止,金屬硫蛋白在哺乳類中共有 4 類 ( MT1 ~ MT4 ), MT1(subtypes A, B, E, F, G, H, L, M, X) 及MT2在大部份動物組織中可見(以肝臟,腎臟最多; 而 MT3及MT4則主要表現在中樞神經系統以及於皮膚及肺臟等的鱗狀上皮細胞 (striated squamous epithelia)中 。由於MT3它是在腦中發現的蛋白,且被認為是與阿茲海默症極具關連性的因子 (Uchida et al, 1991, Chung et al, 2010) 。因此,MT3 除了調控細胞內的金屬平衡外,也俱有其他多樣性的生理病理角色,包括,神經保護,調節氧化壓力,神經細胞組織的鋅離子平衡,腦癌發生,自閉症,帕金昇症。 基於上述,金屬硫蛋白扮演多樣重要的生理平衡及疾病的角色。本研究計畫欲評估及測試人類金屬硫蛋白是否具有改善帕金昇症的效果。同時賦合DHA,期盼可獲得更佳效果。 <br> Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease that leads to severe dementia. The pathogenic signs of AD are characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles which are associated with synaptic loss and neuronal cell death in brains. Inhibition or destabilization of the formation Aβ fibrils in the central nervous system is an attractive therapeutic strategy for treating AD. Additionally, more evidence indicated that increased oxidative stresses may play an important role in AD. Therefore, suppression of the oxidative stresses is a promising approach for AD patient treatment. Metallothionein-3 (MT3) is mainly expressed in the brain tissues crucial for many important homeostasis roles, including free radical scavenge, regulatory zinc metabolism, and detoxification of toxic metals. Moreover, the expression of MT3 was reduced in the brain of AD patients. Therefore, up-regulation of MT3 has been shown a therapeutic potential for neurodegenerative diseases.阿滋海默症金屬硫蛋白抗氧化Alzheimer’s diseasemetallothioneinanti-oxidation優勢重點領域拔尖方案─最具競爭力團隊計畫 【應用金屬硫蛋白第三型於阿茲海默症改善功效之探討】