کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6141319 | 1227234 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of Tat-mediated HIV-1 replication and neurotoxicity by novel GSK3-beta inhibitors
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Inhibition of Tat-mediated HIV-1 replication and neurotoxicity by novel GSK3-beta inhibitors Inhibition of Tat-mediated HIV-1 replication and neurotoxicity by novel GSK3-beta inhibitors](/preview/png/6141319.png)
چکیده انگلیسی
The HIV-1 protein Tat is a critical regulator of viral transcription and has also been implicated as a mediator of HIV-1 induced neurotoxicity. Here using a high throughput screening assay, we identified the GSK-3 inhibitor 6BIO, as a Tat-dependent HIV-1 transcriptional inhibitor. Its ability to inhibit HIV-1 transcription was confirmed in TZM-bl cells, with an IC50 of 40 nM. Through screening 6BIO derivatives, we identified 6BIOder, which has a lower IC50 of 4 nM in primary macrophages and 0.5 nM in astrocytes infected with HIV-1. 6BIOder displayed an IC50 value of 0.03 nM through in vitro GSK-3β kinase inhibition assays. Finally, we demonstrated 6BIO and 6BIOder have neuroprotective effects on Tat induced cell death in rat mixed hippocampal cultures. Therefore 6BIO and its derivatives are unique compounds which, due to their complex mechanisms of action, are able to inhibit HIV-1 transcription as well as to protect against Tat induced neurotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 415, Issue 1, 20 June 2011, Pages 56-68
Journal: Virology - Volume 415, Issue 1, 20 June 2011, Pages 56-68
نویسندگان
Kylene Kehn-Hall, Irene Guendel, Lawrence Carpio, Leandros Skaltsounis, Laurent Meijer, Lena Al-Harthi, Joseph P. Steiner, Avindra Nath, Olaf Kutsch, Fatah Kashanchi,