Taniguchi Taizo, Sumida Miho, Hiraoka Shuko, Tomoo Koji, Kakehi Tomoko, Minoura Katsuhiko, Sugiyama Shigeru, Inaka Koji, Ishida Toshimasa, Saito Naoaki, Tanaka Chikako
Biosignal Research Center, Kobe University, Kobe, Hyogo 657-8501, Japan.
FEBS Lett. 2005 Feb 28;579(6):1399-404. doi: 10.1016/j.febslet.2005.01.039.
Tau is the major antigenic component of neurofibrillary pathology in tauopathy, including Alzheimer's disease. Although conversion of soluble tau to an insoluble polymerized fibrillar form is a key factor in the pathogenesis of tauopathy, the mechanism of the change is unclear and no inhibitors of fibril formation are available. Monoclonal antibodies against the 1st or 2nd repeat of the microtubule binding domain, but not the C-terminal 16 residues, completely inhibited tau aggregation into PHF. Furthermore, they did not inhibit tau-induced tubulin assembly. Thus, they are useful to investigate tau protein conversion and will be useful therapeutic lead materials.
Tau蛋白是包括阿尔茨海默病在内的tau蛋白病中神经原纤维病理的主要抗原成分。尽管可溶性tau蛋白转变为不溶性聚合纤维状形式是tau蛋白病发病机制中的关键因素,但其转变机制尚不清楚,且目前尚无纤维形成抑制剂。针对微管结合结构域第1或第2个重复序列而非C末端16个残基的单克隆抗体,可完全抑制tau蛋白聚集成成对螺旋丝(PHF)。此外,它们并不抑制tau蛋白诱导的微管蛋白组装。因此,它们有助于研究tau蛋白的转化,并且将成为有用的治疗先导材料。