School of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai, 200444, China.
School of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai, 200444, China; University and College Key Lab of Natural Product Chemistry and Application in Xinjiang, School of Chemistry and Environmental Science, Yili Normal University, Yining, 835000, China.
Chem Biol Interact. 2023 Sep 1;382:110631. doi: 10.1016/j.cbi.2023.110631. Epub 2023 Jul 13.
Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.
端粒是位于线性染色体末端的独特结构,负责稳定染色体结构。它们由端粒酶合成,端粒酶是一种逆转录酶核糖核蛋白复合物。人类体细胞中端粒酶活性通常不存在,但在干细胞和生殖细胞中除外。每次细胞分裂时,端粒序列都会缩短,当端粒达到临界限制时,最终导致复制性衰老和细胞凋亡。然而,大多数人类癌细胞表现出增强的端粒酶活性,使其能够持续分裂。端粒酶在癌症和衰老中的重要性使得开发针对端粒酶的药物成为研究的焦点。通过增强端粒相关综合征或疾病中端粒酶的活性,这些药物可以抑制癌细胞生长并延缓衰老。本综述概述了端粒、端粒酶及其在癌症和衰老中的调控,并强调了针对这些领域中端粒酶的小分子药物。