کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8478472 | 1551132 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
tPA promotes cortical neuron survival via mTOR-dependent mechanisms
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کلمات کلیدی
tPAphosphorylated signal transducer and activator of transcription 3mTORPDLp-STAT3Janus kinase - کیناز جانوس JAK/STAT - JAK / STATCell survival - بقای سلولیDIV - دیوdays in vitro - روز in vitropostnatal day 2 - روز بعد از تولد 2tissue plasminogen activator - فعال کننده بافتی پلاسمینوژنTissue plasminogen activator (tPA) - فعال کننده پلاسمینوژن بافتی (tPA)Neuroprotection - محافظت نورونی یا محافظت از عصبmammalian target of rapamycin - هدف پستانداران رپامایسینPoly-d-lysine - پلی دی لیزینJAK - چگونه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Tissue plasminogen activator (tPA) is a thrombolytic agent commonly used in the treatment of ischemic stroke. While the thrombolytic effects of tPA have been well established, the impact of this blood-brain barrier (BBB) crossing drug on neurons is not known. Given the widespread use of tPA in the clinical setting and the strict therapeutic window established for effective use of the drug, we examined the molecular mechanisms mediating the impact of tPA on postnatal cortical neurons isolated from the mouse brain. Dissociated postnatal primary cortical neurons were treated with tPA and the effects on neuron survival were evaluated. Pharmacological inhibitors of several signaling pathways previously implicated in neuroprotection (mTOR, JAK/STAT, MAPK and PKA-dependent mechanisms) were used to pinpoint the mechanistic effectors of tPA on neuron survival in vitro. We report here that tPA treatment results in a time-dependent neuroprotective effect on postnatal cortical neurons that relies predominantly on Janus kinase (JAK) and mammalian target of rapamycin (mTOR) signaling mechanisms. Taken together, these data suggest that tPA promotes neuroprotection in a temporally-regulated manner and that both JAK and mTOR signaling effectors are critical mediators of this neuroprotective effect. The results suggest the possibility of targeting these defined mechanisms to potentially expand the therapeutic window for tPA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 74, July 2016, Pages 25-33
Journal: Molecular and Cellular Neuroscience - Volume 74, July 2016, Pages 25-33
نویسندگان
Julia A. Grummisch, Nafisa M. Jadavji, Patrice D. Smith,