Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Cell Mol Med. 2012 Jan;16(1):1-7. doi: 10.1111/j.1582-4934.2011.01460.x.
Telomeres serve the dual function of protecting chromosomes from genomic instability as well as protecting the ends of chromosomes from DNA damage machinery. The enzyme responsible for telomere maintenance is telomerase, an enzyme capable of reverse transcription. Telomerase activity is typically limited to specific cell types. However, telomerase activation in somatic cells serves as a key step toward cell immortalization and cancer. Targeting telomerase serves as a potential cancer treatment with significant therapeutic benefits. Beyond targeting cancers by inhibiting telomerase, manipulating the regulation of telomerase may also provide therapeutic benefit to other ailments, such as those related to aging. This review will introduce human telomeres and telomerase and discuss pharmacological regulation of telomerase, including telomerase inhibitors and activators, and their use in human diseases.
端粒具有双重功能，既能保护染色体免受基因组不稳定性的影响，又能保护染色体末端免受 DNA 损伤机制的影响。负责端粒维持的酶是端粒酶，一种能够进行逆转录的酶。端粒酶活性通常仅限于特定的细胞类型。然而，体细胞中端粒酶的激活是细胞永生化和癌症的关键步骤。靶向端粒酶是一种具有显著治疗益处的潜在癌症治疗方法。除了通过抑制端粒酶来靶向癌症外，调控端粒酶的调节也可能为其他疾病（如与衰老相关的疾病）提供治疗益处。本综述将介绍人类端粒和端粒酶，并讨论端粒酶的药理学调控，包括端粒酶抑制剂和激活剂及其在人类疾病中的应用。
