廈門大學(xué)生物醫(yī)學(xué)研究院張云武教授和許華曦教授所領(lǐng)導(dǎo)的“福建省神經(jīng)退行性疾病及衰老研究重點實驗室”團隊,，最新鑒定出一個可以抑制老年癡呆癥發(fā)病的小鼠新基因。這項成果目前已被《人類分子遺傳學(xué)》（Human Molecular Genetics）接受并提前在網(wǎng)上發(fā)表,。
繼在代表了國際神經(jīng)生物學(xué)領(lǐng)域研究最高水平的《神經(jīng)元》（Neuron）雜志報道對一個與老年癡呆癥（Alzheimer's disease,，AD）密切相關(guān)的小鼠基因蛋白Rps23r1的鑒定工作以來,，張云武教授和許華曦教授所領(lǐng)導(dǎo)的團隊通過進一步深入研究，鑒定出一個新的Rps23r1同源基因,，具有與Rps23r1相似的功能,，可以通過和腺苷酸環(huán)化酶adenylate cyclase相互作用，促進腺苷酸的合成,，從而提高蛋白激酶A （PKA）的活性,。PKA活性的升高可以抑制糖原合成酶GSK3的活性，進而抑制在AD發(fā)病中起重要作用的Aβ生成和tau蛋白磷酸化,。此外,，該研究還系統(tǒng)探討了Rps23r1基因家族以及Rps23r1的功能結(jié)構(gòu)域。
該論文的第一作者為廈門大學(xué)生物醫(yī)學(xué)研究院“福建省神經(jīng)退行性疾病及衰老研究重點實驗室”的博士生黃秀梅,，通訊作者為張云武教授,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Hum.Mol.Genet. doi: 10.1093/hmg/ddq302
The Rps23rg gene family originated through retroposition of the ribosomal protein s23 mRNA and encodes proteins that decrease Alzheimer's β-amyloid level and tau phosphorylation
Xiumei Huang1,2, Yaomin Chen2, Wu-Bo Li3, Stanley N. Cohen4, Francesca-Fang Liao5, Limin Li3,6, Huaxi Xu1,2 and Yun-wu Zhang1,2,*
1Institute for Biomedical Research and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Xiamen University, Xiamen 361005, China,
2Neurodegenerative Disease Research Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA,
3Functional Genetics, Inc., Gaithersburg, MD, USA,
4Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA,
5Department of Pharmacology, University of Tennessee, Memphis, TN, USA and
6Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking union Medical College, Beijing, China
Retroposition is an important mechanism for gene origination. However, studies to elucidate the functions of new genes originated through retroposition, especially the functions related to diseases, are limited. We recently identified a mouse gene, Rps23 retroposed gene 1 (Rps23rg1), that regulates β-amyloid (Aβ) level and tau phosphorylation, two major pathological hallmarks of Alzheimer's disease (AD), and found that Rps23rg1 originated through retroposition of the mouse ribosomal protein S23 (Rps23) mRNA. Here we show that retroposition of Rps23 mRNA occurred multiple times in different species but only generated another functionally expressed Rps23rg1-homologous gene, Rps23rg2, in mice, whereas humans may not possess functional Rps23rg homologs. Both Rps23rg1 and Rps23rg2 are reversely transcribed relative to the parental Rps23 gene, expressed in various tissues and encode proteins that interact with adenylate cyclases. Similar to the RPS23RG1 protein, RPS23RG2 can upregulate protein kinase A activity to reduce the activity of glycogen synthase kinase-3, Aβ level and tau phosphorylation. However, the effects of RPS23RG2 are weaker than those of RPS23RG1 and such a difference could be attributed to the extra carboxyl-terminal region of RPS23RG2, which may have an inhibitory effect. In addition, we show that the transmembrane domain of RPS23RG1 is important for its function. Together, our results present a new gene family, whose products and associated signaling pathways might prevent mice from developing AD-like pathologies.
