[雙語翻譯]醫(yī)學外文翻譯-- mirna-146在阿爾茨海默氏病中潛在的作用或治療目標？（英文）

1、The potential role of microRNA-146 in Alzheimer’s disease: Biomarker or therapeutic target?Li-Ling Wang a, Yue Huang b, Gang Wang a,?, Sheng-Di Chen a,c,?a Department of Neurology (2) the mechanisms underlying the relat

2、ionship between miR- 146a alterations and the pathological progressive process in AD. Similar questions also arise in the investigations of miR in strokes and other neurological disorders [36,37].Conclusion and perspecti

3、veIn order to determine the physiological functions of miR-146a and b, it is necessary to recognize their potential targets. miR- 146 inhibits a group of genes including IRAK1, TRAF6, CFH, and TSPAN12. We proposed that b

4、oth miR-146a and b are involved in AD pathogenesis via suppressing the above genes and altering their downstream signaling pathways. Initially, miR-146 was identified as a negative feedback regulator in the control of To

5、ll-like recep- tors and cytokine signaling, yet, the suppression of IRAK1-NF-jB signaling mediated by miR-146a eventually caused strong activa- tion of the IRAK2-NF-jB signaling pathway, resulting in enhanced inflammator

6、y response through an unknown mechanism [31]. In addition, the target genes of miR-146, such as ROCK1, EGFR and Notch 1, all play crucial role in cancer. Whether miR-146 mediated inhibition of those genes is involved in

7、the pathogenesis of AD re- mains to be elucidated. In order to expand the knowledge on the function of miR-146 in AD, it is essential to analyze the phenotype of mice with targeted deletion of miR-146a or miR-146b. In su

8、mmary, the functions of miR-146 indicated that it would have applicable potentials on at least two aspects. The first is as a biomarker for the early clinical detection of AD, as its presence in circulating monocytes in

9、adult blood enables easy collection with minimum invasion. In this context, clinically confirmed AD cohort with sufficient case number should be used to evaluate its potential. The other is as a potential therapeutic tar

10、get due to the implications of miR-146a in AD treatment. AD and stressed brain cells associated with a significant down-regulation in miR-146a targets, encoding IRAK1, CFH and TSPAN12 [14,31]. The use of anti-miR-146a to

11、 repress the effects of up-regulated miR-146a may be a potential therapeutic approach. Applying anti-miR- 146a to AD transgenic mouse models is the immediate step towards anti-miR-146a clinical trials for AD.Conflict of

12、interestNone declared.AcknowledgementsThis study was supported by the National Basic Research Devel- opment Program of China (No.2010CB945200), Shanghai KeyDiscipline Program (No.S30202), Shanghai Key Project of Basic Sc

13、i- ence Research (No. 09DZ1950400) and the Program for Outstand- ing Medical Academic Leader (No. LJ 06003).References[1] Duyckaerts C, Delatour B, Potier M. Classification and basic pathology of Alzheimer disease. Acta

14、Neuropathol 2009;118:5–36. [2] Morales I, Farias G, Maccioni R. Neuroimmunomodulation in the pathogenesis of Alzheimer’s disease. Neuroimmunomodulation 2010;17:202–4. [3] Boutajangout A, Quartermain D, Sigurdsson E. Immu

15、notherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 2010;30:16559–66. [4] Jones L, Holmans PA, Hamshere ML, Harold D, Moskvina V, Ivanov D, et al. Genetic evidence impl

16、icates the immune system and cholesterol metabolism in the aetiology of Alzheimer’s disease. PLoS One 2010;5:e13950. [5] Vollmar P, Kullmann JS, Thilo B, Claussen MC, Rothhammer V, Jacobi H, et al. Active immunization wi

17、th amyloid-beta 1-42 impairs memory performance through TLR2/4-dependent activation of the innate immune system. J Immunol 2010;185:6338–47. [6] Lu LF, Liston A. MicroRNA in the immune system, microRNA as an immune syste

18、m. Immunology 2009;127:291–8. [7] Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell 2009;136:26–36. [8] Saba R, Goodman C, Huzarewich RL, Robertson C, Booth S. A miRNA signature of prion i

19、nduced neurodegeneration. PLoS One 2008;3:e3652. [9] Wang WX, Rajeev BW, Stromberg AJ, Ren N, Tang G, Huang Q, et al. The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease p

20、rogression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 2008;28:1213–23. [10] Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. MicroRNA-124 promotes microglia q

21、uiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU 1 pathway. Nat Med 2011;17:64–70. [11] Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146 an in

22、hibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 2006;103:12481–6. [12] Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, et al. Expression of microRNA-146 in rheumatoi

23、d arthritis synovial tissue. Arthritis Rheum 2008;58:1284–92. [13] Aronica E, Fluiter K, Iyer A, Zurolo E, Vreijling J, van Vliet EA, et al. Expression pattern of miR-146a, an inflammation-associated microRNA, in experim

24、ental and human temporal lobe epilepsy. Eur J Neurosci 2010;31:1100–7. [14] Lukiw WJ, Zhao Y, Cui JG. An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain c

25、ells. J Biol Chem 2008;283:31315–22. [15] Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA. Divergent intracellular pathways regulate interleukin-1beta-induced miR- 146a and miR-146b expression and chemo

26、kine release in human alveolar epithelial cells. FEBS Lett 2009;583:3349–55. [16] Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, et al. Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR

27、-146a, a modulator of lymphocyte signaling pathways. J Virol 2008;82:1946–58. [17] Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Ge

28、net 2008;40:43–50. [18] Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One 2007;2:e610. [19] Philippidou D, Schmitt

29、 M, Moser D, Margue C, Nazarov PV, Muller A, et al. Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res 2010;70:4163–73. [20] Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca

30、F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006;103:2257–61. [21] Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC. Expression of mic

31、roRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 2008;27:5643–7. [22] Li Y, Vandenboom TG, Wang Z, Kong D, Ali S, Philip PA, et al. miR-146a suppresses invas

32、ion of pancreatic cancer cells. Cancer Res 2010;70:1486–95. [23] Mei J, Bachoo R, Zhang C. MicroRNA-146a Inhibits Glioma Development by Targeting Notch1. Mol Cell Biol 2011;31:3584–92. [24] Behrens MI, Lendon C, Roe CM,

33、A common biological mechanism in cancer, Alzheimer’s disease?. Curr Alzheimer Res 2006;6:196–204. [25] Roe CM, Behrens MI, Xiong C, Miller JP, Morris JC, Alzheimer disease, et al. Neurology 2005;64:895–8. [26] Roe CM, Fi

34、tzpatrick AL, Xiong C, Sieh W, Kuller L, Miller JP, et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology 2010;74:106–12. [27] Li YY, Cui JG, Hill JM, Bhattacharjee S, Zhao Y, Lukiw WJ. Increased

35、 expression of miRNA-146a in Alzheimer’s disease transgenic mouse models. Neurosci Lett 2011;487:94–8. [28] Sethi P, Lukiw WJ. Micro-RNA abundance and stability in human brain: specific alterations in Alzheimer’s disease