更新于：2024-05-01

TERT

端粒酶逆转录酶

更新于：2024-05-01

基本信息

别名

EST2、HEST2、TCS1

+ [6]

简介

Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.

关联

项与 TERT 相关的药物

Tertomotide hydrochloride

特托莫肽盐酸盐

靶点

TERT

作用机制

TERT抑制剂

在研机构

GemVax & KAEL Co., Ltd. [+1]

原研机构

Pharmexa A/S

在研适应症

胰腺癌 [+3]

非在研适应症

晚期胰腺腺癌 [+7]

最高研发阶段批准上市

首次获批国家/地区

韩国

首次获批日期2014-09-11

Vx-006

靶点

HER2 x MAGEA1 x TERT

作用机制

HER2拮抗剂 [+2]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

hTERT peptide-based vaccine(Invectys SA)

靶点

TERT

作用机制

端粒酶（hTERT）指导的溶细胞作用 [+1]

在研机构

Centre Hospitalier Universitaire de Besancon [+1]

原研机构

Invectys SAS

在研适应症

非小细胞肺癌

非在研适应症

胶质母细胞瘤

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 TERT 相关的临床试验

NCT05303701 / Not yet recruiting临床3期

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Design, Prospective, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Administration of GV1001 1.12 mg/Day in Patients With Moderate to Severe Alzheimer Disease

The objective of this study is to evaluate the safety and efficacy of GV1001 administered subcutaneously in patients with moderate to severe Alzheimer's disease (AD).

开始日期2024-06-01

申办/合作机构

SAMSUNG PHARMACEUTICAL Co., Ltd.

NCT06235775 / Recruiting临床2期

Twelve-months Extension Study to Explore the Long-Term Safety and Efficacy of Subcutaneous Administration of GV1001 1.12 mg/Day in Patients With Progressive Supranuclear Palsy Who Completed Study GV1001-PSP-CL2-011

The study will be conducted by the Sponsor to evaluate Twelve-months Long-Term Safety and Efficacy of GV1001 (1.12 mg) administered subcutaneously as a treatment for Progressive Supranuclear Palsy(PSP). In 75 patients diagnosed with PSP Richardson(PSP-RS) or PSP-Parkinsonism (PSP-P) who Completed Study GV1001-PSP-CL2-011.

开始日期2023-12-12

申办/合作机构

GemVax & KAEL Co., Ltd.

NCT06102525 / Not yet recruiting临床1/2期

A Phase 1/2a, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, and Efficacy of RZ-001 in Combination With Valganciclovir in Subjects With Glioblastoma

This is a Phase 1/2a, open-label study to evaluate the safety, tolerability, immunogenicity, and preliminary clinical activity of RZ-001 administered in combination with VGCV in subjects with hTERT-positive GBM.

开始日期2023-10-01

申办/合作机构

Rznomics Co., Ltd.

100 项与 TERT 相关的临床结果

登录后查看更多信息

100 项与 TERT 相关的转化医学

登录后查看更多信息

0 项与 TERT 相关的专利（医药）

登录后查看更多信息

6,757

项与 TERT 相关的文献（医药）

2024-12-01·Renal failure

Genetic association study of TERT gene variants with chronic kidney disease susceptibility in the Chinese population.

Article

作者: Yan Su ; Yuan Feng ; Xinran Lin ; Chunyang Ma ; Jiali Wei

The incidence and mortality of chronic kidney disease (CKD) are increasing globally. Studies have demonstrated the significance of genetic risk factors in the progression of CKD. Telomerase reverse transcriptase (TERT) may be implicated in the development of CKD. This study aimed to investigate the correlation between TERT gene variants and susceptibility to CKD in the Chinese population. A total of 507 patients with CKD and 510 healthy controls were recruited for this case-control study. Four candidate loci were identified using the MassARRAY platform. Logistic regression analysis was employed to assess the association between TERT gene variants and the risk of CKD. The false positive reporting probability (FPRP) method was utilized to evaluate the validity of statistically significant associations. The multifactorial dimensionality reduction (MDR) method was used to evaluate the interaction between SNPs and the risk of CKD. Furthermore, discrepancies in the clinical features of subjects with diverse genotypes were evaluated using one-way analysis of variance (ANOVA). Our findings revealed a correlation between rs2735940 and rs4635969 and an increased risk of CKD. Stratification analysis indicated that rs4635969 was related to an increased risk of CKD in different subgroups (age ≤ 50 years and male). MDR analysis indicated that the two-site model (rs2735940 and rs4635969) was the best prediction model. Furthermore, the rs2735940 GG genotype was found to be linked to an increased level of microalbuminuria (MAU) in patients with CKD. Our study is the first to reveal a connection between TERT gene variants and susceptibility to CKD, providing new insights into the field of nephrology.

2024-12-01·Bioengineered

Establishment and characterization of a highly metastatic hepatocellular carcinoma cell line.

Article

作者: Jiacheng Huang ; Mengqing Sun ; Menglan Wang ; Anning Yu ; Huilin Zheng ; Chiwen Bu ; Jie Zhou ; Yu Zhang ; Yiting Qiao ; Zhenhua Hu

The prevalence of alcohol-related hepatocellular carcinoma (HCC) has been increasing during the last decade. Cancer research requires cell lines suitable for both in vitro and in vivo assays. However, there is a lack of cell lines with a high in vivo metastatic capacity for this HCC subtype. Herein, a new HCC cell line was established, named HCC-ZJ, using cells from a patient diagnosed with alcohol-related HCC. The karyotype of HCC-ZJ was 46, XY, del (p11.2). Whole-exome sequencing identified several genetic variations in HCC-Z that occur frequently in alcohol-associated HCC, such as mutations in TERT, CTNNB1, ARID1A, CDKN2A, SMARCA2, and HGF. Cell counting kit-8 assays, colony formation assays, and Transwell assays were performed to evaluate the proliferation, migration, and sensitivity to sorafenib and lenvatinib of HCC-Z in vitro. HCC-ZJ showed a robust proliferation rate, a weak foci-forming ability, a strong migration capacity, and a moderate invasion tendency in vitro. Finally, the tumorigenicity and metastatic capacity of HCC-Z were evaluated using a subcutaneous xenograft model, an orthotopic xenograft model, and a tail-veil injection model. HCCZJ exhibited strong tumorigenicity in the subcutaneous xenograft and orthotopic tumor models. Moreover, HCC-ZJ spontaneously formed pulmonary metastases in the orthotopic tumor model. In summary, a new HCC cell line derived from a patient with alcohol-related HCC was established, which showed a high metastatic capacity and could be applied for in vitro and in vivo experiments during pre-clinical research.Highlights• An alcohol-related HCC cell line, HCC-ZJ, was established• HCC-ZJ was applicable for in vitro functional experiment and gene editing• HCC-ZJ was applicable for in vivo tumor growth and spontaneous metastasis models.

2024-05-01·Neural regeneration research

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells.

Article

作者: Yukai Zhang ; Keyong Tian ; Wei Wei ; Wenjuan Mi ; Fei Lu ; Zhenzhen Liu ; Qingwen Zhu ; Xinyu Zhang ; Panling Geng ; Jianhua Qiu ; Yongli Song ; Dingjun Zha

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate (ATP) by supporting cells in the Kölliker's organ. However, the mechanisms responsible for initiating spontaneous ATP release have not been determined. Our previous study revealed that telomerase reverse transcriptase (TERT) is expressed in the basilar membrane during the first postnatal week. Its role in cochlear development remains unclear. In this study, we investigated the expression and role of TERT in postnatal cochlea supporting cells. Our results revealed that in postnatal cochlear Kölliker's organ supporting cells, TERT shifts from the nucleus into the cytoplasm over time. We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo. Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis, suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions. We observed increased ATP synthesis, release and activation of purine signaling systems in supporting cells during the first 10 postnatal days. The phenomenon that TERT translocation coincided with changes in ATP synthesis, release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system. Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

项与 TERT 相关的新闻（医药）

2024-04-04

·GlobeNewswire-Health Care

Ultimovacs to Present Poster at the American Association for Cancer Research (AACR) Annual Meeting 2024

Oslo, April 4, 2024: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology company developing immunotherapeutic cancer vaccines, today announces that the data from the TENDU-101 study in patients with relapse after primary radical prostatectomy (NCT04701021) will be presented in a poster at the 2024 American Association for Cancer Research (AACR), taking place April 5-10, 2024, in San Diego, CA. Additionally, a poster with results related to the Phase I study in prostate cancer (NCT01784913) at Oslo University Hospital will be presented at AACR. The presentation focuses on the changes in transcriptome and TCR-repertoire pre- and post-treatment of hTERT vaccination in combination with androgen deprivation therapy and radiotherapy. Presentation Details: Poster title: CT108 / 16 - Phase I data from TENDU-101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment Session Title: First-in-Human Phase I Clinical Trials 1Date and Time: Monday April 8, 2024, 1:30 – 5:00 PMLocation: Poster Section 48 Poster Board Number: 16Presenter: Sara Mangsbo Clinical trial abstracts are under embargo and will be released at 3:00 PM ET on Friday, April 5. Poster title: 7044 / 11 - Transcriptome and TCR repertoire in human telomerase reverse transcriptase peptide vaccine treated metastatic prostate cancer patients Session Title: Genomics and ImmunooncologyDate and Time: Monday April 10, 2024, 9:00 – 12:30 PMLocation: Poster Section 16 Poster Board Number: 11Presenter: Reetta Nätkin Abstract: https://aacrjournals.org/cancerres/article/84/6_Supplement/7044/737851/Abstract-7044-Transcriptome-and-TCR-repertoire-in ==ENDS== About Ultimovacs Ultimovacs is a clinical-stage biotechnology company developing immunotherapeutic cancer vaccines. The lead cancer vaccine candidate UV1 is an off-the-shelf vaccine directed against human telomerase (hTERT), an antigen present in 85-90% of cancers in all stages of tumor growth. A broad clinical program, with Phase II trials in five cancer indications enrolling more than 670 patients, aims to investigate UV1’s impact in combination with other immunotherapies in multiple cancer types. UV1 is a patented technology owned by Ultimovacs. In addition, Ultimovacs’ adjuvant platform, based on the proprietary Tetanus-Epitope-Targeting (TET) technology, combines tumor-specific antigens and adjuvant in the same molecule and is in Phase I clinical development. The Company is listed on Euronext Oslo Stock Exchange (ULTI). For further information, please contact: Carlos de Sousa, CEO Email: carlos.desousa@ultimovacs.comPhone: +47 908 92507 Anne Worsøe, Head of Investor RelationsEmail: anne.worsoe@ultimovacs.comPhone: +47 90686815 This information is considered to be inside information pursuant to the EU Market Abuse Regulation and is subject to the disclosure requirements pursuant to Section 5-12 in the Norwegian Securities Trading Act.This stock exchange announcement was published by Anne Worsøe, Head of Investor Relations at Ultimovacs ASA, on April 4, 2024, at 07:00 CET.

疫苗临床1期免疫疗法临床2期AACR会议

2024-03-30

·生物探索

Nat Chem Biol | 浙江大学吕志民/许大千揭示代谢酶FBP1调控端粒长度与细胞衰老决定肿瘤生长的新机制

引言端粒功能障碍与衰老过程错综复杂地联系在一起，并作为一个突出的癌症标志而突出。2024年3月27日，浙江大学吕志民及许大千共同通讯在Nature Chemical Biology在线发表题为“Fructose-1,6-bisphosphatase 1 dephosphorylates and inhibits TERT for tumor suppression”的研究论文，该研究证明端粒酶活性在癌症细胞和正常细胞中受到不同的调节，这取决于果糖-1,6-双磷酸酶1 (FBP1)的表达状态。在表达FBP1的细胞中，FBP1直接与端粒酶逆转录酶(TERT)的Ser227位点相互作用并使其去磷酸化。去磷酸化的TERT无法转位到细胞核中，导致小鼠端粒酶活性受到抑制，端粒长度减少，衰老加剧，肿瘤细胞增殖和生长受到抑制。脂质纳米颗粒介导的FBP1 mRNA递送抑制肝脏肿瘤生长。此外，在肾癌和肝癌标本中，FBP1表达水平与TERT pSer227水平呈负相关，并与患者预后不良相关。这些发现表明，FBP1通过其蛋白磷酸酶活性来控制细胞的不朽，并揭示了肿瘤细胞中由于FBP1表达下调或缺乏而产生的独特的端粒酶调节。端粒由重复的TTAGGG核苷酸序列组成，形成一个“帽状结构”，其功能是维持染色体的完整性。端粒在每一轮DNA复制过程中逐渐缩短，端粒功能的丧失导致有丝分裂期间染色体端到端融合，导致双中心染色体的形成和随后染色体断裂的后期桥接。生成的两个子细胞接受不均匀的染色单体，含有两个缺乏端粒的染色单体，导致有丝分裂后的断裂-融合桥(BFB)周期，最终导致正常细胞衰老和凋亡。在癌细胞中，端粒伸长和长度主要依赖于高度激活的端粒酶，在大多数人类癌症中，端粒酶合成端粒重复序列，在5-15%的癌症中，端粒选择性延长(ALT)。端粒酶的活性受端粒酶逆转录酶(TERT)的调控，TERT是端粒酶的催化蛋白亚基，在转录水平和翻译后水平均受调控。TERT磷酸化显著增加端粒酶活性。用于组装具有催化活性的端粒酶，细胞质TERT必须转运到细胞核中，这一过程需要AKT介导的TERT Ser227磷酸化才能将输入蛋白α与TERT8的核定位信号结合。然而，TERT磷酸化和随后的端粒功能在正常细胞和癌细胞中是否受到不同的调节，这在很大程度上是未知的。果糖-1,6-二磷酸酶1 (FBPase 1)是糖异生过程中的限速酶，可将果糖-1,6-二磷酸(F1,6BP)水解为果糖- 6-磷酸(F6P)。在哺乳动物中，两个独立的基因，FBP1和FBP2，分别编码肝脏和肌肉中FBPase的亚型。FBP1主要表达于肝脏和肾脏，在几乎100%的透明细胞肾细胞癌(ccRCC)中普遍缺失，在肝细胞癌(HCC)和其他类型的癌症中经常下调。它的缺乏促进了肝脏肿瘤的进展，并与较差的总生存率和较高的肿瘤复发率相关。研究表明，FBP1与HCC和ccRCC细胞中的缺氧诱导因子(HIFs)或增强子zeste同源物2 (EZH2)以酶活性不依赖的方式相互作用并抑制HIFs。此外，FBP1作为蛋白磷酸酶去磷酸化组蛋白H3来调节基因表达。然而，FBP1的酶活性是否具有直接调节肿瘤细胞增殖的兼职功能尚不清楚。、模式图（Credit: Nature Chemical Biology）该研究证明了FBP1通过FBP1的疏水残基N273与TERT相互作用。FBP1作为蛋白磷酸酶，使TERT的S227位点(pS227)去磷酸化，从而抑制TERT核易位和端粒酶活性，减少端粒长度，抑制肿瘤细胞的增殖和衰老。FBP1蛋白磷酸酶死亡突变体的表达促进了小鼠肿瘤的生长，同时TERT S227磷酸化水平和端粒长度增加。该研究揭示了FBP1蛋白磷酸酶活性对肿瘤和正常细胞中TERT活性差异调节的一个未知的关键机制。低FBP1表达与高TERT S227磷酸化水平以及较短的ccRCC和HCC患者生存期呈负相关，结合lnp为基础的FBP1 mRNA递送有效抑制肿瘤生长，强调了调节蛋白磷酸酶活性和FBP1表达以治疗人类癌症的潜力。原文链接https://www.nature.com/articles/s41589-024-01597-2责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

信使RNA临床结果

2024-03-18

·药渡

全球抗衰药物及靶点最新研发进展

追求长生不老，是人类亘古不变的梦想。抗衰，也成为现代人经久不衰的永恒话题。据统计，2022年全球抗衰老药物市场规模已达670.46亿元（人民币），预测到2028年，全球市场规模将会扩增至1568.71亿元，年均复合增长率约14.86%。目前衰老生物学机制主要分为基因程序性衰老和基因损失理论两大类，基于这两大理论，全球虽未有已上市的专门针对抗衰的药品，但共有14款药物在研（表1），其中临床2期1款、临床1期1款、临床前7款、药物发现5款，涉及的国家地区有美国、中国、韩国、加拿大等，药物类型中小分子药物数量排名第一，共7款。在研抗衰药物目前公开的靶点且处于临床阶段的有TNF-α、SIRT6、GSNOR、TERT + Telomerase和Erα（目前无进展)，下文将对以上靶点的作用机制及代表性药物分别介绍。表1.全球在研抗衰药物1TNF-α（肿瘤坏死因子）TNF-α是一种T细胞和活化的巨噬细胞分泌的多功能细胞因子,在调节细胞免疫反应中起着多种生理和病理作用。TNF-α能够诱导多种细胞的增殖或凋亡,且可与受体结合后通过细胞内多种信号转导途径引发自由基的过量产生等,进而促进机体的衰老；TNF-α在炎症反应中诱发“次级”细胞因子如IL-6、IL-8等的产生,由此激发细胞因子级联反应和炎症连锁反应而损失细胞功能；TNF-α通过炎症连锁反应具有阻抑长时程记忆和神经中毒作用。从结构上看，TNF-α是一种由157个氨基酸组成的同型三聚体蛋白，主要由活化的巨噬细胞、T淋巴细胞和自然杀伤细胞产生。从功能上讲，它可以触发一系列不同的炎症分子，包括其他细胞因子和趋化因子。图1. TNFRs下游的信号形式和生物活性来源：网络公开资料正因为TNF-α能促进机体衰老，所以TNF-α抑制剂也被用于抗衰药物的开发。目前全球共有297款TNF-α上市药物，虽然排名前列的适应症主要为各类免疫疾病，包括类风湿关节炎、强直性脊柱炎、银屑病关节炎、溃疡性结肠炎、葡萄膜炎等，但Science于2021年就刊文表明免疫T细胞能调节机体的健康和寿命，如果阻断由细胞引起的炎症或增加关键代谢分子的供应，就可以减轻机体衰老相关症状的严重程度。研究人员给实验小鼠注射伊那西普（TNF-α抑制剂，阻断T细胞释放TNF-α的药物）后，小鼠的肌肉力量增强、大脑认知功能改善、心脏功能也得改善，由此可见，TNF-α药物在治疗炎症的同时，也能延缓身体衰老。回顾药物研发史，全球首款TNF-α药物英夫利西单于1998年上市，开启了生物治疗RA等免疫疾病的时代，随后国内百奥泰、信达、复宏汉霖等都先后涌入该赛道。2005年，国内首个TNF-α药物——三生国健研发的依那西普生物类似药被批准上市用于治疗自免疾病。弗若斯特沙利文报告显示，中国TNF-α抑制剂市场预计至2030年达到约380亿元，复合年增长率约16.5%，期待已上市的药物一定会有更多抗衰这一新适应症的成果问世。2SIRT6SIRT6又被称为“长寿蛋白”，是一种多功能酶，作为第三家族长寿蛋白中的一员，具有多种催化酶活性，且在抗衰老、染色质调节、转录调控、糖脂代谢、DNA损伤修复等生物学过程中起着重要的作用，因此不少学者认为，激活SIRT6基因能延长人类寿命。相关研究屡见报道，比如2021年布朗大学在PNAS上发表表题为“SIRT6 regulates lifespan in Drosophila melanogaster”的文章，该文章发现dSIRT6在分子和生化水平上与哺乳动物SIRT6的功能非常相似，且dSIRT6过表达可通过对抗Myc的活性延长寿命；2022年东南大学中大医院科学家在Nature Communications 发表文章，表明SIRT6通过抑制 IL-15/JAK3/STAT5信号通路可以减轻软骨细胞衰老，靶向SIRT6有望成为一种非常有前途的治疗骨关节炎的新方法。近期，著名心脏病学家、复旦大学葛均波院士团队，在Aging and Disease上刊发综述文章，阐述了NAD+依赖性酶SIRT6在衰老、代谢、炎症等病理生理过程中发挥的作用，文章主要对三大类SIRT6激活剂的药理作用进行了介绍：其中不乏淫羊藿苷、槲皮素等天然植物提取物，也有NAD+前体（NMN、NR）等分子化合物，还包括SGLT2抑制剂、GLP-1受体激动剂等已上市临床药物，都可能通过激活SIRT6，在改善代谢紊乱、炎症和衰老方面发挥益处，从而对心血管疾病起到治疗效果。就MDL-800药物而言，上海交通大学等研发人员首次证明MDL-800(一种新开发的选择性SIRT6激活剂)通过激活两种DNA修复途径——非同源末端连接(NHEJ)和碱基切除修复(BER)在老鼠源性iPSC中提高基因组稳定性，而且发现用MDL-800预处理通常表现出有限分化潜能的老鼠iPSC促进了由所有三个胚层组成的畸胎瘤的形成,并强烈刺激了嵌合体的产生，表明SIRT6的药理学激活在使用基于iPSC的细胞疗法治疗与衰老相关的疾病方面具有很大的前景（图2）。来源：Aging Cell3GSNORGSNOR（S-亚硝基化谷胱甘肽还原酶）由ADH5基因编码，是乙醇脱氢酶（ADH）家族中的成员。谷胱甘肽一直以来在各美容护肤产品中作为功效成分广为所知，谷胱甘肽是重要的细胞抗氧化物，除了有一定美白效果，也可以改善皮肤老化。2017年的一项研究中受试者补充谷胱甘肽后由紫外线引发的黑斑减少，部分受试者的皮肤皱纹减少且弹性增加。而谷胱甘肽还原酶是利用还原型NAD（P）将氧化型谷胱甘肽（GS－SG）催化反应成还原型（GSH）的酶，目前也被证实在抗衰中发挥有效作用，生物体内的GSNOR能调控多种蛋白的S-亚硝基化，参与多种生理和病理过程。2022年中科院姚永刚团队发表研究成果，在动物模型实验中，GSNOR基因敲除小鼠明显改善了MPTP诱导的帕金森样症状诸如运动障碍、多巴胺神经元的死亡，而敲除GSNOR后，CDK5的S-亚硝基化修饰增加，抑制了CDK5激酶活性，进而抑制CDK5介导的细胞自噬，最终表现为改善了MPTP诱导的帕金森样症状，而且应用GSNOR抑制剂N6022能针对GSNOR靶点进行帕金森样疾病的预防和治疗。2019年北京脑科学与类脑研究中心就刊文，衰老小鼠的海马体中的S-亚硝基谷胱甘肽还原酶（GSNOR）显著增加，而神经元特异性GSNOR转基因小鼠在行为测试中表现出认知障碍，首次发现是GSNOR的增加降低了CREB信号传导因此导致小鼠出现认知障碍，而Nobiletin（川陈皮素）能上调CREB信号通路挽救GSNOR转基因小鼠的认知困难，所以揭开了抗衰药川陈皮素改善衰老认知功能损伤的作用机理。4TERT + Telomerase早在2009年，诺贝尔生理学或医学奖获得者Elizabeth Blackburn、Carol Greider、Jack Szostak就开始了端粒和端粒酶是如何保护染色体的研究，此后端粒也被大众熟知。端粒现在被视为细胞寿命的“有丝分裂钟”，随着年龄增长，DNA损伤的积累会随机影响基因组，而端粒作为覆盖每个染色体臂末端的核蛋白结构，特别易受到增龄性损伤。当端粒因细胞分裂持续缩短时，会加剧体内细胞的凋亡和死亡，最终导致机体衰老，而通过实验干预这一过程，可使细胞规避衰老，并实现无限增殖。有研究表明，通过激活端粒酶逆转录酶（telomerase reverse transcriptase，TERT），可以增加端粒酶的产生，减慢端粒缩短进程，进而延缓衰老。总之，端粒伴随着机体衰老而持续缩短，而通过实验手段干预则可实现延缓衰老。2012年，西班牙著名学者Maria Blasco教授在实验中使用端粒酶逆转录酶基因，成功为小鼠延寿24%，开创了基因疗法抗衰的先河。2015年，时年44岁的美国生物科技公司BioViva的CEO Elizabeth Parrish身先士卒，接受了向自己的细胞中注入TERT基因的实验，该基因能促进细胞生产端粒酶延长端粒长度。经过半年实验期，Parrish的端粒长度从6.71kb增加到7.33kb，换算成细胞生理年龄，大约年轻了20岁。不论该壮举是否是噱头，但端粒检测技术确实在衰老及衰老相关疾病中已有广泛应用。5Erα全球目前仅有一款Erα靶点相关的抗衰药HM-144,且当前状态并无进展。实际上，此前，学界已对ERα的功能进行了广泛深入的研究，尤其在细胞核内调控转录过程中如何影响乳腺癌病程等方面积累了大量工作。研究发现，ERα（核内荷尔蒙受体雌激素受体α，estrogen receptor）在70%乳腺癌病人的体内都处于活化状态，而ERα拮抗剂它莫昔芬在临床上是治疗乳腺癌的一线药物，它可以通过抑制ERα的活性来调节转录过程，延长病人的生存周期。2021年Cell上也刊文称，ERα是一类核质穿梭蛋白（nucleocytoplasmic shuttling protein），可以在细胞核与细胞质之间自由而迅速的移动，ERα被发现可以与多种RNA结合蛋白发生蛋白质相互作用，由此确定ERα亦是一类RNA结合蛋白。在乳腺癌细胞系MCF7 和T47D中， ERα都可以与大量poly(A) RNA相结合，最终支持肿瘤细胞生存和抵抗抗癌药物，再次证实ERα拮抗剂有治疗乳腺癌，延长肿瘤患者生命周期的作用。虽然衰老不可逆转，但庆幸的是，越来越多的药物可以延缓及预防衰老，不论是减少年龄相关的炎症药物、调控能量代谢药物还是直接靶向衰老基因药物或修复损伤基因药物，都可以看到在全球范围内相关研发正如火如荼地开展，期待未来有更多高价值的“长生抗老药”及早上市，满足人们逆龄生长的愿望。参考文献：1.https://www.163.com/dy/article/HOFO2VJA05329KGN.html2.https://zhuanlan.zhihu.com/p/3693134733.https://baijiahao.baidu.com/s?id=1770654033432799807&wfr=spider&for=pc4.https://baijiahao.baidu.com/s?id=1714746913411813252&wfr=spider&for=pc免责声明“药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！

临床1期免疫疗法ASH会议