کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3071035 | 1580756 | 2006 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PTD-XIAP protects against cerebral ischemia by anti-apoptotic and transcriptional regulatory mechanisms
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کلمات کلیدی
permanent MCAOTAT - تاتApoptosis - خزان یاختهایProtein transduction domain - دامنه انتقال پروتئینProtein therapy - درمان با پروتئینStroke - سکته مغزیTranscription factor - عامل رونویسیNeuroprotection - محافظت نورونی یا محافظت از عصبcell penetrating peptide - پپتید نفوذ سلولیcaspase - کسپاز یا کاسپاز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Caspases play a major role in the infarction process that follows occlusion of cerebral arteries and are important targets for stroke therapy. We have generated three fusion proteins that link various domains of the X chromosome-linked inhibitor of apoptosis (XIAP), a potent caspase inhibitor, to the protein transduction domain (PTD) of HIV-1/Tat, and have tested their efficacy after distal occlusion of the middle cerebral artery (dMCAO) in mice. PTD-XIAP failed to accumulate in brain structures after intravenous (iv) delivery, but properly transduced cortical cells when applied topically. Shorter constructs efficiently targeted the lesion after iv delivery. All proteins retained their caspase inhibitory activity and significantly reduced infarct volumes. PTD-XIAP reversed long-term impairments in the water maze test. Sequential activation of transcription factors was observed, suggesting that the effects of XIAP are mediated by both direct inhibition of apoptotic mechanisms and secondary regulation of transcription factors involved in neuronal survival.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 22, Issue 1, April 2006, Pages 177-186
Journal: Neurobiology of Disease - Volume 22, Issue 1, April 2006, Pages 177-186
نویسندگان
Christelle Guégan, Jérôme Braudeau, Cécile Couriaud, Gunnar P.H. Dietz, Pierre Lacombe, Mathias Bähr, Marika Nosten-Bertrand, Brigitte Onténiente,