長(zhǎng)久以來(lái)，科學(xué)家們一直在努力尋找有效地治療阿爾茨海默氏癥（即早老性癡呆癥）的途徑,。最近，美國(guó)研究人員在老鼠體內(nèi)找到一種新的基因Rps23r1,，該基因可減少β淀粉樣蛋白（amyloid beta）和T蛋白（tau）的積累,，從而抑制大腦內(nèi)老年斑的形成和神經(jīng)原纖維纏結(jié)的發(fā)生。研究人員已證實(shí)這種基因在人體細(xì)胞中也存在,。該發(fā)現(xiàn)可能將有助于找到治療阿爾茨海默氏癥的新方法,。相關(guān)研究成果發(fā)表在11月12日《神經(jīng)元》雜志上。
β淀粉樣蛋白和T蛋白在阿爾茨海默氏癥中扮演著關(guān)鍵角色,。大腦中β淀粉樣蛋白產(chǎn)生和積累過多,，會(huì)形成大量老年斑；T蛋白異常磷酸化,，則會(huì)引起腦細(xì)胞內(nèi)的神經(jīng)原纖維纏結(jié),。而大量老年斑和神經(jīng)原纖維纏結(jié),，正是阿爾茨海默氏癥患者大腦功能缺損的主要原因。全世界的科學(xué)家都在尋找減少這兩種蛋白的方法,，以作為治療阿爾茨海默氏癥的一種手段,。所以，找到一種能夠控制兩種蛋白的基因顯得特別重要,。
美國(guó)加利福尼亞州伯納姆醫(yī)學(xué)研究所神經(jīng)退行性疾病研究項(xiàng)目的執(zhí)行主管徐浩喜（音譯）博士和諾貝爾獎(jiǎng)獲得者,、美國(guó)洛克菲勒大學(xué)分子細(xì)胞神經(jīng)科學(xué)研究室教授保羅·格林加德博士及其他研究人員一道,，使用一種稱為隨機(jī)純合基因擾動(dòng)的技術(shù)尋找可調(diào)控淀粉樣蛋白產(chǎn)生的基因,。他們發(fā)現(xiàn)，由Rps23r1基因編碼的Rps23r1蛋白可以與一種叫做腺苷酸環(huán)化酶的蛋白相互作用,，產(chǎn)生一種新蛋白——蛋白激酶A,。蛋白激酶A會(huì)抑制糖原合酶激酶-3（GSK-3）的活動(dòng)，從而調(diào)控淀粉樣蛋白的產(chǎn)生和T蛋白磷酸化,。
研究小組還發(fā)現(xiàn),，Rps23r1是通過逆轉(zhuǎn)錄轉(zhuǎn)座過程被創(chuàng)造出來(lái)的?；蛲ㄟ^信使核糖核酸（mRNA）逆轉(zhuǎn)錄進(jìn)行復(fù)制,，而所得基因副本會(huì)被放置在細(xì)胞DNA的不同位置。雖然大多數(shù)逆轉(zhuǎn)錄轉(zhuǎn)座事件都導(dǎo)致非功能性副本——偽基因的出現(xiàn),，但在極少數(shù)的情況下,，逆轉(zhuǎn)錄基因，就像Rps23r1一樣,，可能會(huì)成為有用的功能基因,。
“從治療阿爾茨海默氏癥的角度看，如果我們能夠在人的大腦細(xì)胞中進(jìn)行這種基因的表達(dá),，我們或許就能控制β淀粉樣蛋白的積累和T蛋白神經(jīng)原纖維纏結(jié),；而從進(jìn)化的角度來(lái)看，逆轉(zhuǎn)錄基因也可以呈現(xiàn)出全新的作用,，我們的發(fā)現(xiàn)就是一個(gè)很好的例子,。”徐浩喜博士說。
研究人員已在轉(zhuǎn)基因阿爾茨海默氏癥小鼠模型上對(duì)Rps23r1減少β淀粉狀蛋白水平和T蛋白磷酸化的效果進(jìn)行了確認(rèn),。同時(shí)他們還確認(rèn),，Rps23r1是老鼠核糖體蛋白s23（Rps23）基因的一個(gè)逆轉(zhuǎn)錄版本，而老鼠的Rps23基因幾乎與人類Rps23基因完全相同,。（生物谷Bioon.com）
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.
