Lee Ming-Hui, Shih Yao-Hsiang, Lin Sing-Ru, Chang Jean-Yun, Lin Yu-Hao, Sze Chun-I, Kuo Yu-Min, Chang Nan-Shan
Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Alzheimers Dement (N Y). 2017 Mar 6;3(2):189-204. doi: 10.1016/j.trci.2017.02.001. eCollection 2017 Jun.
Zinc finger-like protein that regulates apoptosis (Zfra) is a naturally occurring 31-amino-acid protein. Synthetic peptides Zfra1-31 and Zfra4-10 are known to effectively block the growth of many types of cancer cells.
Ten-month-old triple-transgenic (3×Tg) mice for Alzheimer's disease (AD) received synthetic Zfra peptides via tail vein injections, followed by examining restoration of memory deficits.
Zfra significantly downregulated TRAPPC6AΔ, SH3GLB2, tau, and amyloid β (Αβ) aggregates in the brains of 3×Tg mice and effectively restored their memory capabilities. Zfra inhibited melanoma-induced neuronal death in the hippocampus and plaque formation in the cortex. Mechanistically, Zfra blocked the aggregation of amyloid β 42 and many serine-containing peptides in vitro, suppressed tumor necrosis factor-mediated NF-κB activation, and bound cytosolic proteins for accelerating their degradation in ubiquitin/proteasome-independent manner.
Zfra peptides exhibit a strong efficacy in blocking tau aggregation and amyloid Αβ formation and restore memory deficits in 3×Tg mice, suggesting its potential for treatment of AD.
调节细胞凋亡的锌指样蛋白（Zfra）是一种天然存在的由31个氨基酸组成的蛋白质。已知合成肽Zfra1-31和Zfra4-10可有效阻断多种癌细胞的生长。
对10个月大的阿尔茨海默病（AD）三联转基因（3×Tg）小鼠通过尾静脉注射合成Zfra肽，随后检测记忆缺陷的恢复情况。
Zfra显著下调3×Tg小鼠大脑中的TRAPPC6AΔ、SH3GLB2、tau和淀粉样β蛋白（Αβ）聚集体，并有效恢复其记忆能力。Zfra抑制黑色素瘤诱导的海马神经元死亡和皮质斑块形成。从机制上讲，Zfra在体外阻断淀粉样β42和许多含丝氨酸肽的聚集，抑制肿瘤坏死因子介导的NF-κB激活，并结合胞质蛋白以非泛素/蛋白酶体依赖的方式加速其降解。
Zfra肽在阻断tau聚集和淀粉样Αβ形成以及恢复3×Tg小鼠的记忆缺陷方面表现出强大的功效，表明其在治疗AD方面具有潜力。
