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عنوان فارسی مقاله:
مهار پروتئین BET و سیگنالینگ اپی ژنتیک به عنوان یک درمان بالقوه برای پوکی استخوان
عنوان انگلیسی مقاله:
Inhibition of BET proteins and epigenetic signaling as a potential treatment for osteoporosis
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
Bone is a dynamic tissue in constant change through a physiological remodeling process involving bone-specific cells; the osteoclasts which are responsible for the resorption of old or damaged bone and the osteoblasts which are specialized in the formation of a new bone [1,2]. In physiological conditions the balance between bone resorption and bone formation is required to maintain constant bone mass for the majority of adulthood. Disruption of this physiological balance leads to the development of bone-related disorders. Osteoporosis is the most prevalent bone disease in older women and men, characterized by a low bone mass, reduced bone mineral density, and deterioration of bone microarchitecture leading to an increased fracture risk. In osteoporosis the rate of bone resorption exceeds the rate of bone formation, thus decreasing the bone mass [1]. Currently, most available agents in clinical use to treat osteoporosis inhibit bone resorption, whereas only a few stimulate bone formation and restore bone mass [3]. Recent molecular and genetic studies, identifying numerous local and systemic regulators of bone resorption, have considerably improved our molecular knowledge of bone remodeling [4]. Amongst them, epigenetic regulation which include posttranslational histone modifications, miRNA-mediated post-transcriptional regulation and DNA methylation play an important role in bone biology [5,6]. Bromodomain and extra-terminal domain (BET) protein family (BRD2, BRD3, BRD4, and BRDT), through its ability to bind to acetylated lysine on histone tails, is an important class of “histone reading protein” [7]. Bromodomains act as a scaffold for molecular complexes at the recognized histone sites in order to regulate chromatin accessibility to transcription factors and RNA polymerase [8]. Recently, several BET protein inhibitors have been developed including JQ1 and I-BET151. They were described as a new therapeutic approach in various preclinical cancer models [9–13]. In addition, these small-molecule inhibitors of BET proteins were recently identified to suppress bone destruction in many distinct inflammatory diseases (arthritis, periodontitis, bone tumour, osteoporosis) [11,14–16].
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کلمات کلیدی:
Selective inhibition of BET bromodomains. - NCBI - NIH https://www.ncbi.nlm.nih.gov/pubmed/20871596 by P Filippakopoulos - 2010 - Cited by 1397 - Related articles Nature. 2010 Dec 23;468(7327):1067-73. doi: 10.1038/nature09504. Epub 2010 Sep 24. Selective inhibition of BET bromodomains. Filippakopoulos P(1), Qi J, ... BET inhibitor - Wikipedia https://en.wikipedia.org/wiki/BET_inhibitor BET inhibitors are a class of drugs with anti-cancer, immunosuppressive, and other effects in clinical trials in the United States and Europe and widely used in ... Discovery and development · Mechanism of action in cancer Registered report: Inhibition of BET recruitment to chromatin as an ... https://elifesciences.org/content/4/e08997 by JJ Fung - 2015 - Cited by 3 - Related articles Sep 1, 2015 - Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia | The Reproducibility Project: ... Inhibition of BET Recruitment to Chromatin As An Effective Treatment ... www.bloodjournal.org/content/118/21/55 by MA Dawson - 2011 - Cited by 672 - Related articles Inhibition of BET Recruitment to Chromatin As An Effective Treatment for MLL-Fusion Leukaemia. Mark A Dawson, Rab Prinjha, Antje Dittman, George ... Inhibition of BET proteins and epigenetic signaling as a potential ... www.sciencedirect.com/science/article/pii/S8756328216302745 by M Baud'huin - 2017 - Cited by 3 - Related articles This study presents the therapeutic opportunity of BET protein inhibition in osteoporosis. We find that the pharmacological BET protein inhibitor JQ1 rescues ... BET | Constellation Pharmaceuticals https://www.constellationpharma.com › Research & Development Structure-based design used to map the entirety of the BET binding pocket and design best-in-class BET inhibitors. The BET (bromodomain and extra-terminal) ... Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome ... www.cell.com/cell-reports/pdf/S2211-1247(16)30860-9.pdf by AM Kurimchak - Cited by 8 - Related articles Jul 21, 2016 - Inhibition of BET proteins reprograms kinome activity in ovarian cancer cells d. Receptor tyrosine kinase activation overcomes BET inhibition ... Searches related to Inhibition of BET i-bet 762 inhibition of bet recruitment to chromatin as an effective treatment for mll-fusion leukaemia gsk525762 gsk1210151a i-bet151 clinical trial otx-015 cpi-203 cpi-0610
