厦门大学生物医学研究院张云武教授和许华曦教授所领导的“福建省神经退行性疾病及衰老研究重点实验室”团队，最新鉴定出一个可以抑制老年痴呆症发病的小鼠新基因。这项成果目前已被《人类分子遗传学》（Human Molecular Genetics）接受并提前在网上发表。
继在代表了国际神经生物学领域研究最高水平的《神经元》（Neuron）杂志报道对一个与老年痴呆症（Alzheimer's disease，AD）密切相关的小鼠基因蛋白Rps23r1的鉴定工作以来，张云武教授和许华曦教授所领导的团队通过进一步深入研究，鉴定出一个新的Rps23r1同源基因，具有与Rps23r1相似的功能，可以通过和腺苷酸环化酶adenylate cyclase相互作用，促进腺苷酸的合成，从而提高蛋白激酶A （PKA）的活性。PKA活性的升高可以抑制糖原合成酶GSK3的活性，进而抑制在AD发病中起重要作用的Aβ生成和tau蛋白磷酸化。此外，该研究还系统探讨了Rps23r1基因家族以及Rps23r1的功能结构域。
该论文的第一作者为厦门大学生物医学研究院“福建省神经退行性疾病及衰老研究重点实验室”的博士生黄秀梅，通讯作者为张云武教授。（生物谷Bioon.com）
生物谷推荐英文摘要：
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.
