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异位嗅觉受体的功能及其作为药物靶点的研究进展

刘畅, 赵永馨, 葛蓓蓓, 卫彬, 高勇

刘畅,赵永馨,葛蓓蓓,等. 异位嗅觉受体的功能及其作为药物靶点的研究进展[J]. 中国药科大学学报,2024,55(3):412 − 419. DOI: 10.11665/j.issn.1000-5048.2023092001
引用本文: 刘畅,赵永馨,葛蓓蓓,等. 异位嗅觉受体的功能及其作为药物靶点的研究进展[J]. 中国药科大学学报,2024,55(3):412 − 419. DOI: 10.11665/j.issn.1000-5048.2023092001
LIU Chang, ZHAO Yongxin, GE Beibei, et al. Research progress on the function of ectopic olfactory receptors and their value as drug targets[J]. J China Pharm Univ, 2024, 55(3): 412 − 419. DOI: 10.11665/j.issn.1000-5048.2023092001
Citation: LIU Chang, ZHAO Yongxin, GE Beibei, et al. Research progress on the function of ectopic olfactory receptors and their value as drug targets[J]. J China Pharm Univ, 2024, 55(3): 412 − 419. DOI: 10.11665/j.issn.1000-5048.2023092001

异位嗅觉受体的功能及其作为药物靶点的研究进展

基金项目: 国家自然科学基金项目(No.82103318);江苏省自然科学基金项目(No.BK20211112)
详细信息
    通讯作者:

    高勇: Tel:13852388860 E-mail:hayygaoy@njmu.edu.cn

  • 中图分类号: R966

Research progress on the function of ectopic olfactory receptors and their value as drug targets

Funds: This study was supported by the National Natural Science Foundation of China (No. 82103318) and the Natural Science Foundation of Jiangsu Province (No. BK20211112)
  • 摘要:

    嗅觉受体(olfactory receptors,ORs)是一类主要在鼻上皮嗅觉感觉神经元中分布的跨膜蛋白,介导气味向大脑传递实时感觉信号而产生嗅觉。近年来研究发现,ORs也可在鼻腔外组织或器官中表达,且与多种生物过程密切相关,如精子趋化性、伤口愈合、糖脂代谢及肠道分泌等。此外,ORs还与前列腺癌、乳腺癌及结直肠癌等多种恶性肿瘤关系密切,通过调节细胞增殖、凋亡、迁移及侵袭等过程影响肿瘤的发生发展。本文概述了异位ORs对人体组织器官功能的影响,并评估它们作为治疗疾病的药物靶点的潜在价值。

    Abstract:

    Olfactory receptors (ORs) are transmembrane proteins mainly distributed in olfactory sensory neurons of the nasal epithelium, mediating the transmission of real-time sensory signals to the brain to produce smell. Recent studies have reported that ORs can also be expressed in tissues or organs outside the nasal cavity, and are closely related to a variety of biological processes, such as sperm chemotaxis, wound healing, glycolipid metabolism and intestinal secretion. In addition, ORs are closely related to a variety of malignant tumors such as prostate cancer, breast cancer and colorectal cancer, and may affect the occurrence and development of tumors by regulating cell proliferation, apoptosis, migration and invasion. This review provides an overview of the effects of ectopic ORs on the function of various human tissues and organs and assesses their potential value as drug targets for the treatment of human diseases.

  • 嗅觉系统是许多生物赖以生存的重要化学传感系统之一。嗅觉受体(olfactory receptors,ORs)主要分布在嗅觉感觉神经元上,当与特定的气味配体结合时,可激活传统的G蛋白信号通路,促进腺苷酸环化酶(adenylate cyclase,AC)诱导细胞内环磷酸腺苷(cyclic adenosine monophosphate,cAMP)大量分泌,从而触发嗅觉特异性环核苷酸门控阳离子通道来增加Na+及Ca2+离子内流,引起膜电位的改变,将气味的化学信息转化成电信号传递到大脑而产生嗅觉[1]。最初认为ORs仅表达于嗅觉神经元中,但自1992年首次在哺乳动物生殖细胞中发现了鼻黏膜外的第1个OR基因转录本后,大量ORs被发现在睾丸、精子、皮肤、脂肪组织、肠道等多个非嗅觉组织中表达[2],并将这种表达描述为OR的“异位”[3]。近年来,研究表明异位ORs具有多种生物学功能,包括影响精子趋化性[4]、伤口愈合[5]、糖脂代谢[6]、肠道分泌[7]的调控,还参与调控恶性肿瘤的细胞增殖、凋亡、侵袭及转移等过程[8]。此外,ORs属于G蛋白偶联受体(G protein-coupled receptor,GPCR)的一员,目前市场上大约40%的获批靶向药物是以GPCR为靶点[9],鉴于其生物学功能的多样性,使得异位ORs成为具有潜在应用价值的治疗靶点。

    OR基因超家族于1991年由Buck等[10]首次发现,由18个基因家族和150多个亚家族组成[11],其编码的蛋白是分布于细胞膜的含7次跨膜结构域的GPCR。典型的OR基因包含1个短的5-非翻译区(untranslated region,UTR),由1~6个选择性剪接的非编码外显子组成;以及1个长外显子,包含开放阅读框和1个大量的3-UTR[12]。人类基因组包含约400个可编码蛋白质的功能性OR基因[8],OR基因广泛分布在人类基因组中除20号和Y染色体外的所有染色体上[13]。越来越多的研究表明ORs在全身多种组织器官(包括睾丸、精子、脂肪组织、皮肤、胰腺、肝、肺、前列腺、乳腺、肠道等)中表达[14],其表达的数量和水平不尽相同。Feldmesser等[15]通过表达序列标签和微阵列数据分析人类组织中OR转录本的表达,发现在人房室结、皮肤和子宫中ORs表达水平最高。而其他研究表明睾丸组织中ORs表达种类最多,至少有90个不同的ORs[16]。Zhang等[17]则通过使用DNA微阵列芯片检测出非嗅觉组织中表达最多ORs的是肺和心。此外,大量研究还发现一些ORs在肿瘤组织中呈现特异高表达[1821],提示其对恶性肿瘤的发生发展可能起着至关重要的作用。

    鼻上皮内ORs被气味配体激活后产生嗅觉。而异位ORs与嗅觉和神经感觉并无关系,但它们能够通过配体-受体结合影响细胞内信号传导通路来发挥相应的生物学效应,如促进精子趋化性、伤口愈合、糖脂代谢、肠道分泌等。

    异位ORs可能在人类生殖系统中扮演重要角色。一项基因组学分析显示,睾丸中至少有90个不同的ORs表达[16]。Spehr等[22]第一次在人睾丸组织中鉴定出特异性OR——hOR17-4,其能被Bourgeonal激活进而加快精子细胞向卵子的趋化运动速度。Myrac和PI-23472作为各自的气味配体,能激活在睾丸中表达的OR7A5和OR4D1,促进精子细胞向卵子的趋化运动[23]。在人类精子中,Corda等[24]通过GLASS和GPCRdb数据库检索到OR2B2、OR2K2及OR2L2等数10种ORs表达。除此之外,进一步研究发现OR6B2和OR2W3分别位于精子的顶体和鞭毛[16],而OR4S1、OR4C13和OR1I1则主要位于精子的顶体、中段和鞭毛[25]。位于鞭毛和精子中段的ORs最有可能参与精子趋化性,而分布在精子顶体中的ORs则可能参与精子顶体反应和获能,表明ORs分布的不同位置具有不同的功能[26]。受精过程还涉及女性生殖道分泌气味化合物激活精子上的ORs,从而刺激或增强精子对卵巢的趋化性和趋热性[2728]。例如,Teveroni等[29]鉴定出宫颈黏液中富含的短链脂肪酸(short-chain fatty acids,SCFAs)引起OR51E2的活化进而促进精子趋化性。除了在精子趋化性中起重要作用外,ORs还可影响生精过程,促进附睾生长,影响顶体反应,并启动成熟精子中的鞭毛运动,以增强精子-卵母细胞的相互作用[25]

    异位ORs在多种皮肤组织和细胞中表达,如角质形成细胞、黑色素细胞、成纤维细胞及毛囊上皮细胞,涉及不同的皮肤生理过程,如伤口愈合、抗衰老、毛发生长及屏障功能障碍等[5]。OR2AT4可表达于表皮,其在基底层表达最强,并且檀香激活OR2AT4导致细胞Ca2+内流进而诱导cAMP依赖性通路和MAPK/ERK通路,促进角质形成细胞的增殖、迁移和再生,进而参与表皮的伤口愈合[30]。而表达于角质形成细胞的OR2A4/7和OR51B5通过诱导强Ca2+信号和cAMP依赖性通路,促进细胞的分裂增殖、迁移及单层再生,帮助伤口愈合[31]。此外,檀香激活OR2AT4刺激CaMKKβ/AMPK/mTORC1/自噬信号转导来抑制角质形成细胞衰老并促进细胞增殖[32]。人类毛囊细胞中也表达OR2AT4蛋白,檀香刺激OR2AT4可抑制细胞凋亡和增加胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的产生来促进毛发生长[18]和改善体内休止期脱发[33]。Kang等[34]在紫外线照射或炎症条件下发现角质形成细胞中12种异位ORs高表达(OR1F1、OR2A4、OR7D2、OR2AE1、OR2W3、OR2H2、OR5C1、OR10A2、OR10H1、OR52B2、OR52I1及OR52W1),采用特异性配体激活异位ORs可下调皮肤屏障基因的表达,异位ORs可作为皮肤屏障功能异常的生物标志物。这些结果显示,异位ORs调控皮肤生理及病理过程可能为临床皮肤疾病的治疗开辟新途径。

    研究表明,ORs通过调控膳食脂质摄入和脂质代谢参与了体内脂质稳态[6]。特定的气味剂可以激活嗅觉上皮中的ORs影响食欲。这些气味剂的作用通常是由产食欲或厌食性神经肽的分泌变化以及胃迷走神经的活动介导的[35]。例如,Liu等[36]实验证明在禁食条件下,Olfr734作为Asprosin的受体,通过改善小鼠嗅觉性能和激活下丘脑的产食欲调节神经元——刺鼠相关肽表达(agouti-related peptide-expressing,AgRP)神经元而促进摄食行为。此外,异位ORs也参与机体的脂质代谢过程。Olfr544在小鼠的肝和脂肪组织中高表达,并调节细胞能量代谢和肥胖。激活Olfr544诱导脂肪细胞中蛋白激酶A(protein kinase A,PKA)依赖性的脂解,促进肝中的脂肪酸氧化和生酮,其机制与特异性地增加cAMP/PKA/HSL及cAMP/PKA/CREB信号通路有关[37]。Tong等[38]发现OR10J5通过cAMP/PKA/HSL通路减少人肝细胞中甘油三酯的积累参与脂质代谢调节。此外,Olfr43、OR1A1及OR10J5也可通过cAMP/PKA/CREB通路参与调节肝细胞的脂质代谢[3840]。与cAMP/CREB通路平行,OR10J5和Olfr16还通过cAMP/AMPK信号通路减少脂质积累,起到降脂作用[38,41]

    除了参与脂质稳态,异位ORs还可调节葡萄糖代谢。ORs在糖代谢相关的组织中广泛表达,如胰腺、肝、脂肪组织等。此外,ORs在肠道的内分泌细胞及下丘脑的食欲调节神经元中也存在表达[6,42]。例如,Olfr543、Olfr544、Olfr545和Olfr1349等被发现在小鼠胰腺α细胞中高表达,乙酰唑胺激活Olfr544可诱导小鼠胰腺α细胞的Ca2+内流从而增加胰高血糖素的分泌[6]。在胰腺β细胞中,Munakata等[43]发现多达47种ORs亚型,其中Olfr15和Olfr821几乎在每个β细胞中表达。而Leem等[44]发现Olfr15在小鼠胰腺β细胞中高表达,辛酸激活Olfr15上调胰腺β细胞中葡萄糖激酶表达而增加葡萄糖摄取并刺激胰岛素分泌。Cheng等[45]报道了Olfr109作为胰岛素受体,感知内源性胰腺肽或变性胰岛素来激活Gi/cAMP信号通路进而抑制胰腺β细胞的胰岛素分泌。作为肠道内分泌细胞的一种,L细胞可分泌胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1),激活OR1A1及OR1G1可诱导L细胞的GLP-1分泌,并通过AC/cAMP等多种途径调节胰岛β细胞的功能,刺激胰岛素分泌[46]。在饥饿条件下,肠道分泌Famsin结合Olfr796以促进葡萄糖的产生进行能量动员[47]。类似情况,Olfr734作为Asprosin受体在空腹时调节肝葡萄糖的产生,维持葡萄糖稳态[48]。因此,探索异位ORs对糖脂代谢的影响及其调控机制,揭示了其在肥胖、糖尿病等代谢病中起重要作用。

    肠道上皮内包含多种内分泌细胞如肠嗜铬细胞和L细胞等,可通过异位ORs作为化学传感器感知SCFAs和肠道微生物代谢物等并分泌一系列激素,如YY肽、GLP-1和血清素等,参与肠道稳态的调节[7,49]。Braun等[50]报道了17个在人肠嗜铬细胞中表达的异位ORs,包括OR73、hOR17-7/11、OR1G1和hOR17-210等,激活上述ORs后可促进血清素的释放来促进肠道蠕动和分泌。Nishida等[51]发现Olfr78在小鼠结肠和肠内分泌细胞系STC-1中大量表达,口服低聚果糖产生的SCFAs通过激活Olfr78诱导小鼠肠道YY肽的分泌来维持肠道菌群的稳态。而Dinsart等[52]发现SCFA配体醋酸盐激活Olfr78促进肠嗜铬细胞分化而维持结肠稳态。Wu等[53]发现激活Olfr544不仅诱导cAMP/PKA/CREB信号轴而增加GLP-1的分泌,还可调节肠道微生物和代谢物改善结肠炎症。Kotlo等[54]发现Olfr78在三硝基苯磺酸或葡聚糖硫酸钠诱导的小鼠结肠炎模型中表达下调,表明Olfr78及其人直系同源嗅觉受体OR51E2可能在肠道炎症中起作用。这些研究都表明异位ORs通过影响肠道分泌、菌群稳态及代谢物等调节肠道稳态,为炎性消化道疾病的治疗提供了潜在策略。

    动脉粥样硬化是一种动脉壁炎症性疾病,由脂质代谢失调和持续的不良免疫反应引起。巨噬细胞积累正常和修饰的脂蛋白导致动脉壁形成泡沫细胞,并与先天免疫受体的激活有关,包括NOD样和Toll样受体,导致炎症和斑块进展[55]。NOD样和Toll样受体识别病原体及损伤相关分子时启动NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体,诱导白细胞介素-1β(interleukin-1β,IL-1β)分泌[56]。Orecchioni等[57]发现Olfr2和人直系同源嗅觉受体OR6A2分别表达在小鼠和人的巨噬细胞中,当受到辛醛刺激时,Olfr2/OR6A2可激活NLRP3炎症小体,诱导巨噬细胞分泌IL-1β并驱动动脉粥样硬化。然而,在缺乏Olfr2的小鼠中注射辛醛却不会加速动脉粥样硬化[58]。可见,靶向异位ORs有望成为预防和治疗动脉粥样硬化的新策略。

    恶性肿瘤是严重威胁人类健康的高发病率和高病死率疾病。因此,肿瘤的早期诊断和探寻新的治疗靶点就显得尤为重要。近年来研究显示异位ORs在肝癌、乳腺癌、前列腺癌和膀胱癌等多种恶性肿瘤中呈现差异表达,并参与肿瘤细胞的增殖、凋亡、侵袭及转移等过程[8]。总之,异位ORs在肿瘤的发生发展过程中起到重要作用,可成为潜在的治疗靶点。

    前列腺癌是男性最常见的恶性肿瘤,前列腺特异性G蛋白偶联受体(prostate specific G protein coupled receptor,PSGR)又称OR51E2,其在前列腺癌中高表达并与肿瘤进展密切相关[59]。Rodriguez等[60]发现过表达PSGR通过AKT介导的NF-κB激活诱导前列腺慢性炎症反应,导致低级别前列腺上皮内瘤变的发生。Sanz等[61]研究证明激活PSGR通过PI3Kγ依赖性信号通路促进前列腺癌细胞的侵袭与转移。Xu等[62]的研究进一步证明OR51E2通过Gβγ/PI3Kγ/ARF1途径激活ERK1/2及MAPK介导前列腺癌细胞的恶性进展。Rodriguez等[63]发现在PTEN缺失的前列腺癌中,过表达PSGR增加细胞增殖,而敲低PSGR抑制细胞增殖和迁移,结果表明PSGR过表达可协同PTEN缺失加速前列腺癌的进展。

    一项基于生物信息学的研究发现OR2B6在73%乳腺癌细胞系和80%乳腺癌组织中高表达,而在健康组织中没有检测到OR2B6,其在乳腺癌组织呈现癌细胞的独特染色模式[8]。另外一项对浸润性乳腺癌患者ORs转录物丰度分析的研究发现,OR2W3、OR2B6与乳腺癌进展相关[19]。OR2T6与OR51J1被证明在乳腺癌组织中过表达,并且与乳腺癌患者的不良预后相关[20,64],能通过激活EMT和MAPK/ERK通路促进乳腺癌的进展[20]。此外,Li等[21]发现OR5B21在乳腺癌中高表达,并通过STAT3/NF-κB/CEBPβ信号轴诱导乳腺癌细胞迁移、侵袭。

    Kalbe等[65]证明了OR2J3在非小细胞肺癌细胞系A549中高表达,配体Helional结合OR2J3激活PI3K信号通路,促进胞质内Ca2+释放和ERK的磷酸化,诱导细胞凋亡、抑制细胞增殖和迁移。OR51E1在肺类癌细胞系NCI-H727和NCI-H720以及肺类癌肿瘤组织中高表达,可能是肺类癌诊断的新靶点[3]。OR51E2同源类似物Olfr78缺陷小鼠的Lewis肺癌移植瘤生长减慢和转移减少,同时抗肿瘤免疫细胞群能力增加[66]

    Weber等[67]发现OR51B4在结肠癌细胞系HCT116和人结肠癌组织中高表达,并通过改变p38 MAPK、mTOR及AKT的磷酸化水平抑制细胞增殖、迁移,诱导细胞凋亡。Morita等[68]发现OR7C1在维持结肠癌干细胞的干性中具有重要作用,OR7C1高表达增强人群的致瘤性并与结肠癌患者的不良预后相关。Maßberg等[69]发现肝癌细胞系Huh2细胞中的OR1A2激活不仅通过激活cAMP依赖的信号通路导致胞质Ca2+水平升高,而且还诱导p38 MAPK的磷酸化来降低细胞增殖能力,揭示OR1A2可作为肝癌诊断和治疗的潜在靶点。

    Shibel等[70]发现OR5H2在人子宫内膜癌细胞系USPC-1和USPC-2中表达,并通过与IGF-1信号通路相互作用调节子宫内膜癌细胞增殖。Gelis等[71]发现OR51E2在黑色素瘤细胞中高表达,OR51E2与β-紫罗兰酮结合后抑制细胞增殖、迁移并诱导细胞凋亡。Cho等[72]发现一部分ORs显示出神经胶质瘤亚型特异性表达,并且OR51E1和OR2C1可作为预测胶质瘤预后的潜在生物标志物。

    GPCR在人体组织中广泛表达,它们通过与细胞外配体结合并将信号转导到各种细胞内偶联分子来控制多种生理反应[73]。靶向GPCR药物在于寻找新的GPCR配体或者调节剂以抑制或激活GPCR功能[74]。类似于GPCR药理学模型,ORs药物靶点在于寻找激动剂或抑制剂使其处于“开”或“关”状态[75]。OR2AT4在人的头皮毛囊中表达,用特异性激动剂Sandalore诱导OR2AT4能减少细胞凋亡和增加外根鞘中IGF-1来延长人类头发的体外生长。相反,特异性OR2AT4拮抗剂Phenirat与Sandalore共同给药时能逆转IGF-1的上调并抑制头发生长[18]。有趣的是,有初步的临床试验表明在应用含Sandalore的洗发水12周后降低了约20%的脱发[14]。这些结果表明,ORs可能代表治疗脱发的新治疗靶点。钠葡萄糖共转运蛋白1(sodium glucose cotransporters 1,SGLT1)在葡萄糖的肠道吸收和肾再吸收中发挥重要作用[76]。Olfr1393在肾近端小管中特异性表达,Schiazza等[77]发现Olfr1393基因敲除小鼠表现出肾近端小管中SGLT1表达降低,从而导致尿葡萄糖减少和葡萄糖耐量的改善。因此靶向Olfr1393在未来可能具有临床意义,因为在没有Olfr1393的情况下能改善小鼠的葡萄糖耐量,但是该途径成功的关键是鉴定出Olfr1393拮抗剂。类似情况,OR激动剂在肿瘤中得到了大量的应用,如结直肠癌中的Troenan[67]、肺癌中的乙酰醛[65]以及肝癌中的香茅醛等[69](详见表1)。

    表  1  异位嗅觉受体潜在药物靶点研究现状
    受 体 配 体 产生效应 目标疾病或症状 生物学功能 参考文献
    OR2AT4 檀香 激活 伤口愈合 增加角质细胞增殖、迁移、再生和伤口愈合 [30,7879]
    激活 脱发 增加头发生长和延长毛囊的生长期 [18,33]
    Olfr544 壬二酸 激活 肥胖和皮下脂肪减少 通过脂肪分解和肝脂肪酸氧化而减少皮下脂肪 [37]
    OR51B6 Troenan 抑制 结肠癌 抑制细胞增殖和迁移 [14,67]
    OR1A2 单萜(–)-香茅醛 抑制 肝癌 抑制细胞增殖 [69]
    OR2J3 乙酰醛 抑制 肺癌 诱导细胞凋亡、抑制细胞增殖和迁移 [65]
    OR51E2 β-紫罗兰酮 抑制 黑色素瘤 抑制黑色素细胞增殖、迁移并诱导细胞凋亡 [71]
    下载: 导出CSV 
    | 显示表格

    靶向异位受体需要识别作为选择性激动剂或拮抗剂的配体。目前由于大部分OR还没有明确的配体,故关于OR的药物靶点通常聚焦于天然配体上[80]。如上述所提出的檀香,它可以很容易地传递到皮肤上,促进伤口愈合和头发生长[30,33]。除此之外,肽与OR结合可能具有重要意义,因为肽在全身具有良好的生物利用度,并且对受体的亲和力高于大多数气味剂。Asprosin(一种肽激素)对Olfr734的亲和力比OR对通常气味剂的亲和力高出约1000倍[58]。现如今,多肽激活GPCR的生理作用在临床实验中正获得越来越多的关注。迄今为止,已有近50种GPCR肽类药物获得批准[81]。肽与OR的高效结合也进一步证明OR可能成为良好的药物靶标。

    然而,根据组织分布和异位受体的可及性,需要特定形式的气味传递。此外,由于气味剂是小而易挥发的分子,可能与多个ORs结合,并且具有中等至高的微摩尔亲和力,导致它们可能不是靶向异位ORs的理想药理学试剂。另一种思路是寻找这些异位ORs的内源性激活配体。Yoshikawa等[82]使用分级分离方法来筛选各种组织提取物中的天然ORs配体,从而鉴定出脂肪酸代谢物可能是气味受体的生理配体激动剂,但其能否发挥功能还需进一步验证。目前为止,体外研究已经确定了多个ORs的受体与配体对,对于确定的异位ORs及其生理功能,就能开发高亲和力配体的筛选,如小分子药物和内源性配体。其他策略也可用于靶向异位ORs,如针对受体的抗体可以抑制内源性配体结合或用于药物递送,嵌合抗原受体T细胞疗法也可用于靶向表达异位ORs的肿瘤细胞。尽管目前OR尚未有广泛的药理学数据相关联的研究,但未来ORs有望成为疾病治疗的重要靶点。

    ORs不应再被视为纯粹的气味受体,而是参与整个人体生理与病理过程的化学感受器。ORs在鼻外组织器官中广泛表达,尤其是代谢活跃的组织器官(包括睾丸、卵巢、肠道、胰腺和脂肪组织)及恶性肿瘤组织。这些异位ORs在不同组织或细胞中通过触发多种信号转导发挥不同调节功能。随着对异位ORs功能认识加深,其在多种疾病诊断和治疗等方面具有潜在的临床应用价值,包括恶性肿瘤、皮肤疾病、代谢疾病及消化道炎性疾病等。总而言之,异位ORs的生理功能及其作为药物靶点仍有待深入探索。

  • 表  1   异位嗅觉受体潜在药物靶点研究现状

    受 体 配 体 产生效应 目标疾病或症状 生物学功能 参考文献
    OR2AT4 檀香 激活 伤口愈合 增加角质细胞增殖、迁移、再生和伤口愈合 [30,7879]
    激活 脱发 增加头发生长和延长毛囊的生长期 [18,33]
    Olfr544 壬二酸 激活 肥胖和皮下脂肪减少 通过脂肪分解和肝脂肪酸氧化而减少皮下脂肪 [37]
    OR51B6 Troenan 抑制 结肠癌 抑制细胞增殖和迁移 [14,67]
    OR1A2 单萜(–)-香茅醛 抑制 肝癌 抑制细胞增殖 [69]
    OR2J3 乙酰醛 抑制 肺癌 诱导细胞凋亡、抑制细胞增殖和迁移 [65]
    OR51E2 β-紫罗兰酮 抑制 黑色素瘤 抑制黑色素细胞增殖、迁移并诱导细胞凋亡 [71]
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-09-19
  • 网络出版日期:  2024-06-24
  • 刊出日期:  2024-06-24

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