https://transhumanist.ru/index.php?action=history&feed=atom&title=BTK 2026-04-12T16:17:39Z История изменений этой страницы в вики MediaWiki 1.43.6 https://transhumanist.ru/index.php?title=BTK&diff=6015&oldid=prev 2021-05-12T15:05:52Z

<p>Новая страница: «Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) [AGMX1] [ATK] [BPK]...»</p> <p><b>Новая страница</b></p><div>Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) [AGMX1] [ATK] [BPK]<br /> <br /> ==Publications==<br /> <br /> {{medline-entry<br /> |title=Amelioration of age-related brain function decline by Bruton&#039;s tyrosine kinase inhibition.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31736210<br /> |abstract=One of the hallmarks of aging is the progressive accumulation of senescent cells in organisms, which has been proposed to be a contributing factor to age-dependent organ dysfunction. We recently reported that Bruton&#039;s tyrosine kinase ([[BTK]]) is an upstream component of the p53 responses to DNA damage. [[BTK]] binds to and phosphorylates p53 and [[MDM2]], which results in increased p53 activity. Consistent with this, blocking [[BTK]] impairs p53-induced senescence. This suggests that sustained [[BTK]] inhibition could have an effect on organismal aging by reducing the presence of senescent cells in tissues. Here, we show that ibrutinib, a clinically approved covalent inhibitor of [[BTK]], prolonged the maximum lifespan of a Zmpste24 progeroid mice, which also showed a reduction in general age-related fitness loss. Importantly, we found that certain brain functions were preserved, as seen by reduced anxiety-like behaviour and better long-term spatial memory. This was concomitant to a decrease in the expression of specific markers of senescence in the brain, which confirms a lower accumulation of senescent cells after [[BTK]] inhibition. Our data show that blocking [[BTK]] has a modest increase in lifespan in Zmpste24 mice and protects them from a decline in brain performance. This suggests that specific inhibitors could be used in humans to treat progeroid syndromes and prevent the age-related degeneration of organs such as the brain.<br /> <br /> |keywords=* BTK<br /> * cellular senescence<br /> * healthspan<br /> * p53<br /> * progeria<br /> |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974713<br /> }}<br /> {{medline-entry<br /> |title=[[BTK]] suppresses myeloma cellular senescence through activating AKT/P27/Rb signaling.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28915637<br /> |abstract=We previously explored the role of [[BTK]] in maintaining multiple myeloma stem cells (MMSCs) self-renewal and drug-resistance. Here we investigated the elevation of [[BTK]] suppressing MM cellular senescence, a state of irreversible cellular growth arrest. We firstly discovered that an increased expression of [[BTK]] in MM samples compared to normal controls by immunohistochemistry (IHC), and significant chromosomal gain in primary samples. In addition, [[BTK]] high-expressing MM patients are associated with poor outcome in both Total Therapy 2 (TT2) and TT3 cohorts. Knockdown [[BTK]] expression by shRNA induced MM cellular senescence using β-galactosidase (SA-b-gal) staining, cell growth arrest by cell cycle staining and decreased clonogenicity while forcing [[BTK]] expression in MM cells abrogated these characteristics. We also validated this feature in mouse embryonic fibroblast cells (MEFs), which showed that elevated [[BTK]] expression was resistant to MEF senescence after serial cultivation [i]in vitro[/i]. Further mechanism study revealed that [[BTK]] activated AKT signaling leading to down-regulation of P27 expression and hindered RB activity while AKT inhibitor, LY294002, overcame [[BTK]]-overexpression induced cellular senescence resistance. Eventually we demonstrated that [[BTK]] inhibitor, CGI-1746, induced MM cellular senescence, colony reduction and tumorigenecity inhibition [i]in vivo[/i]. Summarily, we designate a novel mechanism of [[BTK]] in mediating MM growth, and [[BTK]] inhibitor is of great potential [i]in vivo[/i] and [i]in vitro[/i] suggesting [[BTK]] is a promising therapeutic target for MM.<br /> <br /> |keywords=* AKT<br /> * BTK<br /> * CGI-1746<br /> * multiple myeloma<br /> * senescence<br /> |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593608<br /> }}</div>

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