廈門大學(xué)生物醫(yī)學(xué)研究院許華曦教授和張云武教授最新研究鑒定出一個小鼠基因蛋白Rps23r1,，并發(fā)現(xiàn)該蛋白可以抑制與老年癡呆癥（Alzheimer's disease, AD）發(fā)病密切相關(guān)的生化過程,。這一研究為開發(fā)治療老年癡呆癥的藥物提供了新的靶點,，并為人類與小鼠之間在老年癡呆癥發(fā)生上的差異提供了可能的解釋。該成果目前已被《神經(jīng)元》雜志收錄并發(fā)表（廈門大學(xué)為第一作者單位）,。
大量實驗證據(jù)表明Ab的大量生成是引發(fā)老年癡呆癥的關(guān)鍵原因,，而tau蛋白的高度磷酸化也參與了某些神經(jīng)退行性疾病的發(fā)生,。因此鑒定那些能夠影響Ab產(chǎn)生和tau蛋白磷酸化的新基因蛋白并闡明其作用機理,，對于開發(fā)治療這些疾病的藥物,，具有非常重要的意義。
通過與洛克菲勒大學(xué)的諾貝爾獎得主Paul Greengard教授,、斯坦福大學(xué)的美國科學(xué)院院士Stanley N. Cohen教授,、Functional Genetics公司的Limin Li博士及Burnham研究所的科學(xué)家們的多年合作研究，許教授和張教授的實驗室應(yīng)用隨機同源基因干擾技術(shù)（Random Homozygous Gene Perturbation）在小鼠細(xì)胞中篩選,、鑒定出Rps23r1基因,，并通過細(xì)胞實驗和轉(zhuǎn)基因動物模型，證實了Rps23r1蛋白對Ab生成和tau磷酸化的抑制作用,。此外,，過表達(dá)Rps23r1還增加了神經(jīng)突觸，表明其能夠有所改善老年癡呆癥轉(zhuǎn)基因小鼠的學(xué)習(xí)記憶,。更重要的是,，研究組發(fā)現(xiàn)Rps23r1不僅在小鼠細(xì)胞內(nèi)起作用,，而且在人源細(xì)胞內(nèi)也同樣發(fā)揮功能，這說明人體內(nèi)也具有該基因所介導(dǎo)的信號通路,，可以作為藥物開發(fā)的潛在靶點,。
另一方面,，與人類隨著年齡的老化會易患老年癡呆癥不同,，老齡的野生型小鼠不會出現(xiàn)老年癡呆癥的病理特征。先前的研究認(rèn)為這可能是由于小鼠的Ab序列與人的Ab序列不同的緣故,。許教授和張教授的這項研究發(fā)現(xiàn)了Rps23r1基因在小鼠中的起源,，而在人類中還沒有發(fā)現(xiàn)Rps23r1的同源基因。因此如果人類中的確沒有Rps23r1同源基因的話,，兩位教授的發(fā)現(xiàn)就為人與小鼠的老年癡呆癥發(fā)病差異提供了另一種可能的解釋,，即小鼠基因組中特異性地存在著某些保護(hù)性的基因如Rps23r1，可以保護(hù)小鼠不發(fā)生老年癡呆癥,，這將為預(yù)防人類老年癡呆癥開拓一個新的研究方向,。（生物谷Bioon.com）
廈門大學(xué)最新研究成果：
Science：RIP3具有細(xì)胞凋亡/細(xì)胞壞死開關(guān)作用
Lab Chip：玻璃芯片中的微米級肺泡
JCB：Wnt信號通路調(diào)節(jié)機制
JBC：Arx蛋白質(zhì)在細(xì)胞核定位分子機理及調(diào)控方式研究
Nature Cell Biology：蛋白分子Axin可在細(xì)胞受損后控制p53基因表達(dá)
Oncogene：肺癌細(xì)胞表觀遺傳學(xué)研究
生物谷推薦原始出處：
Neuron, Volume 64, Issue 3, 328-340, 12 November 2009 doi:10.1016/j.neuron.2009.08.036
A Functional Mouse Retroposed Gene Rps23r1 Reduces Alzheimer's β-Amyloid Levels and Tau Phosphorylation
Yun-wu Zhang1, 2, 8, Shijie Liu2, 8, Xue Zhang2, 8, Wu-Bo Li3, 8, Yaomin Chen2, Xiumei Huang1, 2, Liangwu Sun2, Wenjie Luo4, William J. Netzer4, Richard Threadgill3, Gordon Wiegand3, Ruishan Wang1, 2, Stanley N. Cohen5, Paul Greengard4, Francesca-Fang Liao2, 7, Limin Li3, 6, , and Huaxi Xu2, ,
1 Institute for Biomedical Research and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Xiamen University, Xiamen 361005, China
2 Neurodegenerative Disease Research Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
3 Functional Genetics, Inc., Gaithersburg, MD 20878, USA
4 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA
5 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
6 Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking union Medical College, Beijing 100005, China
7 Department of Pharmacology, University of Tennessee Health Science Center College of Medicine, Memphis, TN 38163, USA
Senile plaques consisting of β-amyloid (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau are major pathological hallmarks of Alzheimer's disease (AD). Elucidation of factors that modulate Aβ generation and tau hyperphosphorylation is crucial for AD intervention. Here, we identify a mouse gene Rps23r1 that originated through retroposition of ribosomal protein S23. We demonstrate that RPS23R1 protein reduces the levels of Aβ and tau phosphorylation by interacting with adenylate cyclases to activate cAMP/PKA and thus inhibit GSK-3 activity. The function of Rps23r1 is demonstrated in cells of various species including human, and in transgenic mice overexpressing RPS23R1. Furthermore, the AD-like pathologies of triple transgenic AD mice were improved and levels of synaptic maker proteins increased after crossing them with Rps23r1 transgenic mice. Our studies reveal a new target/pathway for regulating AD pathologies and uncover a retrogene and its role in regulating protein kinase pathways.
