title: New insights in amyloid beta interactions with human telomerase.
abstract: It is well-known that aging is the most risk factor for Alzheimer's disease (AD). Recent studies have demonstrated that human telomerase is associated with pathological mechanisms of AD. In view of the central role of telomere and telomerase in the aging process, herein we found that the aggregated form Aβ (Aβ1-40 and Aβ1-42), not Aβ monomer, could inhibit telomerase activity both in vitro and in living cells. The β-sheet structures were essential for Aβ-induced telomerase inhibition. Further studies indicated Aβ oligomers inhibited telomerase activity through binding to DNA·RNA hybrid formed by telomeric DNA and the RNA template of telomerase, then blocking telomerase elongation of telomeric DNA. We also identified that intracellular Aβ localized at telomere, and induced cell senescence and telomere shortening. These results indicate that Aβ oligomers can be potential natural inhibitors of telomerase and that inhibition of telomerase activity may be one of the factors for Aβ-induced cytotoxicity. Our work may offer a new clue to a better understanding of aging and AD.
authors.affiliation: Laboratory of Chemical Biology and Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Changchun, Jilin 130022, China.
authors.forename: Jiasi
authors.initials: J
authors.lastname: Wang
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Zhao
authors.forename: Andong
authors.initials: A
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ren
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Qu
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D019098:Telomerase