Telomere biology disorders: time for moving towards the clinic?
Telomere biology disorders: time for moving towards the clinic?
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DOI：
10.1016/j.molmed.2022.08.001
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发表时间：
2022-10
影响因子：
13.6
通讯作者：
Parker, Roy
中科院分区：
文献类型：
--
作者：
Batista, Luis F. Z.;Dokal, Inderjeet;Parker, Roy
端粒生物学障碍（TBD）是一组由损害端粒维持的突变引起的罕见疾病。在大多数TBD患者中发现了导致TERC/hTR（端粒酶RNA组分）水平降低的突变，包括hTR本身、hTR结合蛋白（NOP 10、NHP 2、NAF 1、ZCCHC 8和DKC 1）和hTR加工所需蛋白（PARN）的功能缺失突变。这些患者表现出不同的临床表现，最常见的包括骨髓衰竭/再生障碍性贫血、肺纤维化和肝硬化。对于患有TBD的患者没有治愈性疗法。对hTR生物发生、成熟和降解的理解已经确定了靶向聚（A）聚合酶PAPD 5和TGS 1的途径和药理学试剂，PAPD 5将3'寡腺苷尾添加到hTR以促进hTR降解，TGS 1修饰hTR的5'帽结构以增强降解，作为可能的治疗方法。接下来的关键步骤是临床试验，旨在确定这些化合物在TBD患者中的有效性和潜在副作用。
Telomere biology disorders (TBDs) are a group of rare diseases caused by mutations that impair telomere maintenance. Mutations that cause reduced levels of TERC/hTR, the telomerase RNA component, are found in most TBD patients and include loss of function mutations in hTR itself, hTR binding proteins (NOP10, NHP2, NAF1, ZCCHC8 and DKC1), and proteins required for hTR processing (PARN). These patients show diverse clinical presentation that most commonly include bone marrow failure/aplastic anemia, pulmonary fibrosis and liver cirrhosis. There are no curative therapies for patients suffering with TBDs. An understanding of hTR biogenesis, maturation and degradation has identified pathways and pharmacological agents targeting the poly(A) polymerase PAPD5, which adds 3’ oligoadenosine tails to hTR promoting hTR degradation, and TGS1, which modifies the 5’ cap structure of hTR to enhance degradation, as possible therapeutic approaches. Critical next steps are clinical trials aimed at establishing the effectiveness and potential side effects of these compounds in TBD patients.
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影响因子：
64.8
作者：
Batista, Luis F. Z.;Pech, MatthewF.;Zhong, Franklin L.;Nguyen, Ha Nam;Xie, Kathleen T.;Zaug, Arthur J.;Crary, Sharon M.;Choi, Jinkuk;Sebastiano, Vittorio;Cherry, Athena;Giri, Neelam;Wernig, Marius;Alter, Blanche P.;Cech, Thomas R.;Savage, Sharon A.;Pera, Renee A. Reijo;Artandi, Steven E.
通讯作者：
Artandi, Steven E.
DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1074/jbc.rev120.014017
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Grill S;Nandakumar J
通讯作者：
Nandakumar J
影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
DOI：
10.1098/rstb.2003.1370
发表时间：
2004-01-29
影响因子：
6.3
作者：
Chan, SRWL;Blackburn, EH
通讯作者：
Blackburn, EH