预约演示

更新于：2024-11-01

TRAF6

更新于：2024-11-01

基本信息

别名

E3 ubiquitin-protein ligase TRAF6、Interleukin-1 signal transducer、RING finger protein 85

+ [5]

简介

E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 (PubMed:31620128, PubMed:11057907, PubMed:18347055, PubMed:19713527, PubMed:19465916). Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (PubMed:19675569). Leads to the activation of NF-kappa-B and JUN (PubMed:16378096, PubMed:17135271, PubMed:17703191). Seems to also play a role in dendritic cells (DCs) maturation and/or activation (By similarity). Represses c-Myb-mediated transactivation, in B-lymphocytes (PubMed:18093978, PubMed:18758450). Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor (PubMed:8837778, PubMed:19825828, PubMed:12140561). Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation (By similarity). Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production (By similarity). Participates also in the TCR signaling by ubiquitinating LAT (PubMed:25907557, PubMed:23514740).

关联

项与 TRAF6 相关的药物

Delmitide

靶点

IFNγ x IL-2 x IRAK4 x MYD88 x TRAF6

作用机制

IFNγ抑制剂 [+4]

在研机构-

原研机构

Genzyme Corp.

在研适应症-

非在研适应症

巴雷特食管 [+12]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRAF6 相关的临床结果

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100 项与 TRAF6 相关的转化医学

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0 项与 TRAF6 相关的专利（医药）

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3,642

项与 TRAF6 相关的文献（医药）

2025-05-01·Neural Regeneration Research

The complex effects of miR-146a in the pathogenesis of Alzheimer’s disease

Article

作者: Cui, Guohong ; Liu, Jiajia ; Guo, Haidong ; Wang, Yu ; Long, Yunfan

Alzheimer’s disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities. Neuroinflammatory plaques formed through the extracellular deposition of amyloid-β proteins, as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins, comprise two typical pathological features of Alzheimer’s disease. Besides symptomatic treatment, there are no effective therapies for delaying Alzheimer’s disease progression. MicroRNAs (miR) are small, non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological processes. Indeed, miR-146a, a NF-κB-regulated gene, has been extensively implicated in the development of Alzheimer’s disease through several pathways. Research has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this disorder. MiR-146a is believed to reduce amyloid-β deposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway; however, there is also evidence supporting that it can promote these processes through many other pathways, thus exacerbating the pathological manifestations of Alzheimer’s disease. It has been widely reported that miR-146a mediates synaptic dysfunction, mitochondrial dysfunction, and neuronal death by targeting mRNAs encoding synaptic-related proteins, mitochondrial-related proteins, and membrane proteins, as well as other mRNAs. Regarding the impact on glial cells, miR-146a also exhibits differential effects. On one hand, it causes widespread and sustained inflammation through certain pathways, while on the other hand, it can reverse the polarization of astrocytes and microglia, alleviate neuroinflammation, and promote oligodendrocyte progenitor cell differentiation, thus maintaining the normal function of the myelin sheath and exerting a protective effect on neurons. In this review, we provide a comprehensive analysis of the involvement of miR-146a in the pathogenesis of Alzheimer’s disease. We aim to elucidate the relationship between miR-146a and the key pathological manifestations of Alzheimer’s disease, such as amyloid-β deposition, tau protein hyperphosphorylation, neuronal death, mitochondrial dysfunction, synaptic dysfunction, and glial cell dysfunction, as well as summarize recent relevant studies that have highlighted the potential of miR-146a as a clinical diagnostic marker and therapeutic target for Alzheimer’s disease.

2025-01-01·Journal of Ethnopharmacology

Comparable clinical advantages identification of three formulae on rheumatic disease using a modular-based network proximity approach

Article

作者: Xiong, Wei ; Zong, Wenjing ; Niu, Qikai ; Li, Xin ; Tong, Lin ; Wang, Pengqian ; Zeng, Ziling ; Wang, Jing’ai ; Tian, Siwei ; Zhang, Siqi ; Li, Bing ; Cai, Qiujie ; Zhang, Huamin ; Zhang, Yanqiong ; Xu, Haiyu ; Wang, Jing'ai ; Zheng, Danping

ETHNOPHARMACOLOGICAL RELEVANCEHerbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue.AIM OF THIS STUDYTo develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae.MATERIALS AND METHODSIn this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments.RESULTS32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = -20.26); YXB was significantly associated with AS (Z = -4.532), MI (Z = -29.11), RhFv (Z = -6.945), OA (Z = -39.97), and GA (Z = -13.03); and WBFK was significantly associated with MI (Z = -205.5), SLE (Z = -37.65), RhFv (Z = -42.45), and GA (Z = -17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments.CONCLUSIONSThe modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment.

2024-12-31·Renal Failure

Astragaloside IV relieves passive heymann nephritis and podocyte injury by suppressing the TRAF6/NF-κb axis

Article

作者: Lu, Guoyuan ; Hu, Yuwen ; Zhao, Min ; Ruan, Yilin ; Ma, Yuhua ; Ke, Yanrong ; Jiang, Xiaocheng ; Wang, Yuxin ; Shi, Manman

The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

项与 TRAF6 相关的新闻（医药）

2024-08-12

·生物谷

上海中医药大学季光/国海东团队揭示负载miR-146a的牛奶外泌体靶向治疗心肌缺血再灌注损伤的作用及机制

近日，上海中医药大学季光教授和国海东研究员团队在Journal of Nanobiotechnology上发表研究论文Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury。该研究探讨了负载miR-146a的牛奶外泌体对心肌缺血再灌注损伤（MIRI）的治疗作用，并证实负载miR-146a的牛奶外泌体经靶向肽修饰后具有更好的疗效。这一发现为临床治疗MIRI提供新的策略和方法。再灌注治疗对于在心肌梗死后挽救心肌是至关重要的，但是恢复血流的过程本身会加剧对心肌的损伤。这种现象被称为MIRI。已知微小RNA-146a（miR-146a）对心肌损伤后心脏功能改善具有潜在影响。然而，以特定和有效的方式将miR-146a递送至心脏仍然是一个挑战。牛奶外泌体（MEs）有可能是miRNA治疗的理想递送平台。在这项研究中，研究人员以MEs为载体，通过电穿孔将miR-146成功装载至MEs中（MEs-miR-146a），经灌胃给予MIRI大鼠治疗后，发现其可以减少心肌组织凋亡和炎症因子的表达，并且在改善MIRI后的心功能方面显示出有益的效果。为了提高MEs-miR-146a静脉注射后对心肌损伤部位的靶向性，研究人员研发了由缺血心肌靶向肽（IMTP）修饰的功能化MEs系统（IMTP-MEs-miR-146a）。静脉注射IMTP-MEs-miR-146a后，心肌组织中的miR-146a水平显著增加，提示IMTP修饰增强了负载于MEs中的miR-146a向心肌损伤部位的靶向递送，并显示出有效抑制炎症反应，从而在全身给药后发挥更好的治疗作用。因此，IMTP修饰的MEs被证明是用于靶向心脏损伤治疗的miRNA的实用药物递送系统。此外，MEs-miR-146a可以负向调节NF-κB信号通路，降低TRAF6和IRAK1的表达，通过抑制IRAK1/TRAF6/NF-κB信号通路发挥其抗炎作用。综上所述，MEs-miR-146a是一种有前途的治疗MIRI的策略，经IMTP修饰后具有更好的疗效，有望在未来应用于临床实践。上海中医药大学中西医结合学院博士后孟婉婷为论文第一作者，季光教授、国海东研究员和牟芳芳副教授为共同通讯作者。该研究得到国家自然科学基金、上海自然科学基金和上海市学术带头人项目的资助支持。论文链接： Meng WT, Zhu J, Wang YC, et al. Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury. J Nanobiotechnology. 2024;22(1):382. Published 2024 Jul 1. doi:10.1186/s12951-024-02631-0 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

临床结果专利侵权

2024-07-10

·CPHI制药在线

天然活性成分治疗阿尔茨海默病研究进展（下篇）

关注并星标CPHI制药在线随着现代化分离鉴定技术的不断优化，从天然产物中筛选发现高效、高选择性、低毒性的靶向抗AD活性成分成为抗AD药物研发的重要途径之一。上篇介绍了多糖类、皂苷类、酚类和黄酮类等天然成分的抗AD作用，本文继续介绍醌类、苯丙素类、萜类、生物碱类和内酯类等天然成分的抗AD作用。相关阅读：《天然活性成分治疗阿尔茨海默病研究进展（上篇）》 5 醌类大黄酸是大黄中的蒽醌类成分，可通过上调SIRT1/过氧化物酶体增殖物激活受体γ 共激活因子-1α（PGC-1α）途径改善线粒体功能，缓解氧化应激，降低AD小鼠脑内Aβ病理和神经炎症。番泻叶苷A 能够减轻AD中的细胞凋亡、铁死亡、氧化应激和炎症，其作用机制与抑制肿瘤坏死因子受体相关因子6（TRAF6）/NF-κB轴相关。紫草素是从紫草中提取的萘醌类化合物，研究发现紫草素可能通过抑制NF-κB/MAPKs信号通路，减轻D-半乳糖（D-gal）诱导的衰老小鼠模型的空间学习记忆障碍、氧化应激、炎症和神经元损伤。 6 苯丙素类毛蕊花糖苷源自肉苁蓉，能够通过阻断NF-κB通路抑制神经炎症，改善能量代谢，减少Aβ 沉积和Tau过磷酸化，抑制ERS减少细胞凋亡等途径发挥神经保护作用。反式桂皮醛大量存在于肉桂等植物体内，可降低AD小鼠脑内p-Tau水平，抑制神经炎症，改善NMDAR介导的突触功能障碍。厚朴酚是厚朴的主要活性成分，能够通过调节PI3K/Akt和NF-κB信号通路抑制神经炎症和突触功能障碍，并促进神经元和小胶质细胞自噬，抑制β-和γ-分泌酶活性，增强Aβ 降解酶活性，从而抑制Aβ 沉积和细胞凋亡，改善AD小鼠记忆障碍。连翘酯苷A提取自连翘的干燥果实，研究发现连翘酯苷A可显著增强AD小鼠脑内多巴胺能信号，抑制铁沉积和脂质过氧化，通过靶向激活Nrf2/GPX4轴调节铁死亡介导的神经炎症，发挥抗AD 特性。 7 萜类芍药苷普遍存在于芍药科植物中，芍药苷可通过抑制 p53介导铁死亡增强AD小鼠的认知和行为能力。京尼平苷酸能够激活PI3K/Akt/生长相关蛋白43（GAP43）调节轴，缓解AD病程中Aβ 积累、神经元凋亡、炎症和轴突损伤。梓醇是地黄的主要活性成分之一，能够减轻Aβ沉积和神经炎症，改善AD小鼠的认知能力。体外研究发现，梓醇可以通过上调去整合素金属蛋白酶（ADAM）10 表达减少Aβ 生成，并能减轻BBB 破坏，促进可溶性Aβ跨 BBB外排清除。疟疾药物青蒿素可通过降低病理蛋白的表达、抗氧化、抗炎、抗凋亡等途径改善AD小鼠的认知能力。广藿香醇可通过调节APP的加工抑制Aβ斑块沉积，减轻Tau蛋白过磷酸化、神经炎症和肠道菌群失调，改善AD小鼠焦虑相关行为缺陷和认知障碍。此外，广藿香醇还可作为选择性雌激素受体β（ERβ）激动剂，促进MG 吞噬Aβ，改善突触完整性，有效减轻雌性APP/PS1小鼠的学习记忆障碍。丹参酮ⅡA被广泛应用于治疗心血管疾病。研究表明，丹参酮ⅡA在体内和体外均可发挥较强的抗AD 作用，包括促进 Aβ转运，降低 Tau 磷酸化水平，逆转胆碱能系统功能障碍，抑制氧化应激、炎症反应及凋亡等。雷公藤红素提取于雷公藤的根皮部，可激活转录因子 EB（TFEB）介导的自噬，促进磷酸化Tau 聚集体的降解，明显改善记忆缺陷。黄芪甲苷通过增加PPARγ表达，抑制神经炎症并减少APP裂解生成Aβ，改善大鼠认知学习能力。 8 生物碱类生物碱是主要存在于植物中的一种含氮碱性化合物及少量具有明显生物活性但不含碱性的含氮有机化合物。石杉碱甲是生物碱类抗AD新药，是一种高效高选择性的中枢AChE抑制剂。临床前试验证实石杉碱甲对一系列认知障碍模型动物的学习和记忆均有改善作用。石杉碱甲除了抑制AChE 活性外，还可通过调节APP加工及减少海马体中Aβ累积等途径对神经产生保护作用。同时还可降低淀粉样蛋白结合醇脱氢酶（ABAD）水平且进一步降低Aβ 和ABAD复合物水平从而缓解APP/PS1小鼠的线粒体功能障碍。黄连素可以抑制细胞外淀粉样斑块及细胞内神经纤维缠结，还可以促进受损神经的轴突延伸和轴突再生，用于治疗神经退行性疾病。紫堇总生物碱可以升高AD模型大鼠的SOD、CAT 水平，降低ROS、MDA、IL-1β、TNF- α水平，降低 Aβ、NF-κB 蛋白的表达，增加MAP2蛋白的表达。金钗石斛总生物碱可通过增加Aβ 的清除、激活自噬活性、上调Klotho，从而对SAMP8小鼠与衰老相关的认知功能缺损、神经元衰老、损伤和丢失具有保护作用。还可通过增加海马和皮层中 BDNF、GDNF和CNTF的表达减少神经元凋亡及突触丢失，改善Aβ诱导的小鼠空间学习和记忆障碍。吴茱萸碱可减少AD小鼠脑内Aβ42的沉积，增加血清中Aβ42的水平，但对 Aβ40无显著影响，此外吴茱萸碱还能抑制氧化应激，在AD小鼠中枢胆碱能系统中，吴茱萸碱可显著升高血清中ACh和胆碱乙酰转移酶的水平，降低血清、下丘脑和大脑中乙酰胆碱酯酶的水平。苦参碱和氧化苦参碱均是从苦参中提取的生物碱，一定条件下可相互转化。研究发现，苦参碱可抑制Aβ 聚集，阻断RAGE的配体结合位点减弱Aβ刺激下RAGE通路的激活，减轻 Aβ诱导的神经毒性和炎症反应。同样的，氧化苦参碱也具有抗神经炎症的作用，其抗炎活性与其调控MAPKs和NF-κB 信号通路有关。异钩藤碱通过抑制c-Jun氨基末端激酶（JNK）信号通路的激活，减少Aβ 生成和沉积、Tau过度磷酸化和神经炎症，从而改善AD 小鼠的认知障碍。小檗碱从黄连中分离而得，研究发现小檗碱能够通过激活Nrf2并增加下游信号级联反应，减少异常铁积累和脂质过氧化产物抑制铁死亡，减轻AD小鼠脑内Aβ 斑块、Tau蛋白过度磷酸化和神经元丢失。 9 内酯类研究表明1，6-O，O-二乙酰旋覆花内酯可以减轻LPS诱导的BV-2小胶质细胞的神经炎症反应，减轻6月龄5x FAD小鼠的认知障碍、还能显著降低AD小鼠脑组织中淀粉样斑块的积累、Aβ的表达、Tau 蛋白的磷酸化和BACE1 的表达。双氢青蒿素（DHA）可改善 APP/PS1 小鼠记忆和认知功能障碍，减少β淀粉样斑块沉积，降低Aβ40和Aβ42水平，改善APP/PS1 小鼠大脑神经元过度凋亡。雷公藤甲素能改善Aβ注射小鼠的空间学习及记忆，降低Aβ的表达，此外，雷公藤甲素还能降低Aβ42注射小鼠炎症细胞因子的表达，降低氧化损伤。银杏内酯B能改善SAMP8小鼠的认知功能障碍，与氧化应激、炎症和核转录因子E2相关因子2/谷胱甘肽过氧化物酶4（GPX4）介导的铁死亡途径的减弱有关。藁本内酯是当归挥发油的主要成分，具有抑制小胶质细胞的激活和促炎细胞因子产生的作用，对神经炎症具有一定的治疗作用。穿心莲内酯能够调节AD患者血清的IL-1β、IL-6及TNF-α水平，减轻炎性反应。白果内酯和银杏内酯B 均源自银杏叶中，白果内酯能够抑制信号转导及转录激活因子3（STAT3）依赖的炎症细胞因子的释放，并促进Aβ 降解酶的表达，以挽救神经元缺陷。银杏内酯B通过自噬降解途径抑制NLRP3炎症小体的激活，减轻AD小鼠神经炎症和认知障碍。天然产物类型多样，药理活性广泛，一直以来是新药研发的重要源头。但是，目前在天然产物成分治疗AD 领域仍存在一些不足之处，如天然产物中化学成分的复杂性使得其活性成分和作用机制难以准确确定，研究和开发过程相对较为困难；其次，中药制剂的质量和含量难以保证，可能导致不同批次之间的差异，影响临床疗效的稳定性；另外，尽管许多中药被传统上用于治疗认知障碍，但其科学验证和临床疗效仍需要更多严格的随机对照研究支持，以及药物相互作用，一些天然产物成分可能与化学药物相互作用，影响药物代谢和疗效，需要更多关于安全性的研究，一些天然抗AD活性成分存在生物利用度低、难以透过血脑屏障等问题，需进一步结构修饰和优化，或采用剂型改造和联合用药等方法，提高对靶点的选择性与抗AD疗效等。参考资料 [1]黄丹蓉,程亚敏,冯紫涵,等.基于靶点机制的抗阿尔茨海默病天然活性成分研究进展[J].天然产物研究与开发,2023,35(10):1808-1819. [2]曹珊,陈智慧,秦静琪,等.中药及其有效成分治疗阿尔茨海默病研究进展[J].中国实验方剂学杂志,2024,30(10):258-268. [3]杜正彩,胡润华,李瑞林,等.治疗阿尔茨海默病中药化学成分及机制的研究概况[J].中国实验方剂学杂志,2024,30(05):236-245. 作者简介：小米虫，药品质量研究工作者，长期致力于药品质量研究及药品分析方法验证工作，现就职于国内某大型药物研发公司，从事药品检验分析及分析方法验证。 END 【智药研习社抗体系列直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床结果

2024-03-26

·生物谷

Nature子刊 | 食补太慢？研究发现利用特定光线照射骨组织可促进骨骼自我修复

喝牛奶有助于骨骼长得又粗又壮，但如果直接照射光线也有帮助呢？如今，在一项新的研究中，来自日本东京医科齿科大学的研究人员报告说，利用光线照射骨组织有助于治疗骨病。他们发现，基于光线的治疗方法可以帮助激活骨骼进行自我修复。相关研究结果近期发表在Scientific Reports期刊上，论文标题为“Development of an optogenetics tool, Opto-RANK, for control of osteoclast differentiation using blue light”。骨骼在破骨细胞（osteoclast）和成骨细胞（osteoblast）的作用下不断重塑，其中破骨细胞负责分解骨组织，而成骨细胞负责生成新的骨组织。这两类细胞都是从未成熟的前体细胞发育而来，控制它们的活动是治疗骨骼生长障碍的一种很有前景的方法。论文共同通讯作者 Takao Nakata 说，“以前的研究已经使用了光遗传学，即通过光激活目标分子来诱导或增强特定的细胞功能。然而，光遗传学工具尚未被用于由前体细胞分化而形成的成熟分化细胞，比如由单核细胞/巨噬细胞产生的破骨细胞。”在这项新的研究中，这些作者构建了RANK的光激活形式，其中RANK是破骨细胞分化过程中的一种重要信号蛋白。然后，他们在巨噬细胞中表达了这种名为Opto-RANK的光遗传蛋白，并用蓝光照射激活它，观察这些巨噬细胞是否会开始表现得像破骨细胞。图片来自Scientific Reports, 2024, doi:10.1038/s41598-024-52056-w论文共同通讯作者 Tomohiro Ishii 解释说，“这些结果非常明显。Opto-RANK对蓝光激活的反应是形成活性簇，从而招募TRAF6，即一种调节破骨细胞分化的关键分子。”此外，这些蓝光激活的巨噬细胞还表现出三个基因的激活，这些基因通常在成熟的破骨细胞中表达。这些巨噬细胞还形成了许多小坑，这是成熟破骨细胞的一个特征，有助于它们分解骨组织。Nakata说，“我们的研究结果表明，Opto-RANK可用于诱导巨噬细胞分化为破骨细胞，并在蓝光激活下刺激局部骨吸收。”蓝光激活可以实现对 Opto-RANK 活性的精确控制，这使其成为细胞疗法的有力工具，例如治疗异常钙化疾病和牙齿矫正问题。此外，Opto-RANK 的作用可能超出骨生物学的范畴，因为 RANK 信号还涉及其他重要功能，如免疫、体温调节和肿瘤发生。参考资料：Aiko Takada et al. Development of an optogenetics tool, Opto-RANK, for control of osteoclast differentiation using blue light. Scientific Reports, 2024, doi:10.1038/s41598-024-52056-w.Opto-RANK: A light switch for osteoclasts that could activate bone repairhttps://medicalxpress.com/news/2024-03-opto-osteoclasts-bone.html本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

细胞疗法