Tacr2,也称为Tachykinin receptor 2 (NK2R),是一种编码神经激肽受体2的基因。神经激肽是一类神经肽,包括物质P、神经激肽A和神经激肽B,它们与NK1、NK2和NK3受体结合。Tacr2编码的NK2受体是一种G蛋白偶联受体,主要在哺乳动物的中枢神经系统中表达。该受体在多种生理和病理过程中发挥重要作用,包括生殖、胃肠道运动、分泌、内脏感觉、情绪调节和免疫系统功能[1,2,3,4,5,6,7,8]。
在抑郁症的病理生理学中,Tacr2基因的表达和DNA甲基化水平的变化引起了研究者的关注。有研究发现,慢性不可预测的轻度应激(CUMS)会导致大鼠海马体中Tacr2基因表达的增加和DNA甲基化水平的降低,这表明Tacr2基因的表达可能与抑郁症的病理生理学有关[1]。此外,有研究发现,Tacr2基因的表达与前列腺癌的临床特征和疾病-free生存相关,Tacr2的表达水平与临床分期、Gleason评分和生存结果显著相关[3]。这些结果表明,Tacr2基因可能在多种疾病的发生和发展中发挥重要作用。
在遗传学研究中,Tacr2基因的遗传多态性也引起了研究者的关注。有研究发现,Tacr2基因的SNPs与阿尔茨海默病(AD)没有关联,这表明Tacr2基因可能不是AD的主要易感基因[2]。此外,有研究发现,人类TACR2基因中存在两种氨基酸改变SNPs,编码NK2受体蛋白的Ile23Thr和Arg375His变异体,这些变异体在人群中具有较高的频率,但它们并不影响内源性激动剂神经激肽A(NKA)或小分子拮抗剂saredutant和ZD6021的细胞内Ca2+信号通路的效力[9]。
综上所述,Tacr2基因编码的NK2受体在多种生理和病理过程中发挥重要作用。Tacr2基因的表达和DNA甲基化水平的变化与抑郁症、前列腺癌等疾病的发生和发展有关。此外,Tacr2基因的遗传多态性也可能影响其功能。进一步研究Tacr2基因的功能和调控机制,有助于深入理解其在疾病发生和发展中的作用,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Xiang, Dan, Xiao, Jiawei, Fu, Linyan, Wang, Gaohua, Liu, Zhongchun. 2019. DNA methylation of the Tacr2 gene in a CUMS model of depression. In Behavioural brain research, 365, 103-109. doi:10.1016/j.bbr.2019.01.059. https://pubmed.ncbi.nlm.nih.gov/30711443/
2. Friedrich, P, Feulner, T M, Laws, S M, Förstl, H, Riemenschneider, M. 2009. No association of Tachykinin receptor 2 (TACR2) polymorphisms with Alzheimer's disease. In Neurobiology of aging, 32, 544-5. doi:10.1016/j.neurobiolaging.2009.03.007. https://pubmed.ncbi.nlm.nih.gov/19375820/
3. Jianfeng, Wang, Yutao, Wang, Jianbin, Bi. 2021. TACR2 is associated with the immune microenvironment and inhibits migration and proliferation via the Wnt/β-catenin signaling pathway in prostate cancer. In Cancer cell international, 21, 415. doi:10.1186/s12935-021-02126-0. https://pubmed.ncbi.nlm.nih.gov/34364377/
4. Torres, Encarnacion, Velasco, Inmaculada, Franssen, Delphine, Romero-Ruiz, Antonio, Tena-Sempere, Manuel. 2021. Congenital ablation of Tacr2 reveals overlapping and redundant roles of NK2R signaling in the control of reproductive axis. In American journal of physiology. Endocrinology and metabolism, 320, E496-E511. doi:10.1152/ajpendo.00346.2020. https://pubmed.ncbi.nlm.nih.gov/33427049/
5. Mao, Y-L, Shen, C-L, Zhou, T, Xu, W-X, Wang, Z-G. 2017. Ablation of Tacr2 in mice leads to gastric emptying disturbance. In Neurogastroenterology and motility, 29, . doi:10.1111/nmo.13117. https://pubmed.ncbi.nlm.nih.gov/28585346/
6. Blasco, Víctor, Pinto, Francisco M, Fernández-Atucha, Ainhoa, Fernández-Sánchez, Manuel, Candenas, Luz. 2022. Female Infertility Is Associated with an Altered Expression Profile of Different Members of the Tachykinin Family in Human Granulosa Cells. In Reproductive sciences (Thousand Oaks, Calif.), 30, 258-269. doi:10.1007/s43032-022-00998-9. https://pubmed.ncbi.nlm.nih.gov/35739351/
7. Zhang, Ke, Chen, Que T, Li, Jing H, Li, Jia L, Drew, Paul A. 2016. The expression of tachykinin receptors in the human lower esophageal sphincter. In European journal of pharmacology, 774, 144-9. doi:10.1016/j.ejphar.2016.02.014. https://pubmed.ncbi.nlm.nih.gov/26852958/
8. Nation, J B, Cabot-Miller, Justin, Segal, Oren, Lucito, Robert, Adaricheva, Kira. 2021. Combining Algorithms to Find Signatures That Predict Risk in Early-Stage Stomach Cancer. In Journal of computational biology : a journal of computational molecular cell biology, 28, 985-1006. doi:10.1089/cmb.2020.0568. https://pubmed.ncbi.nlm.nih.gov/34582702/
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