کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6022155 | 1580658 | 2014 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity following spinal cord injury
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کلمات کلیدی
Spinal cord injury - آسیب نخاعیNeurite growth - رشد نوریتtissue plasminogen activator - فعال کننده بافتی پلاسمینوژنType 1 plasminogen activator inhibitor - مهار کننده فعال کننده پلاسمینوژن نوع 1Neuroplasticity - نوروپلاستیNeurocan - نوروکانChondroitin sulfate proteoglycans - پروستاگلایسینهای سولفات کلسترول
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Although tissue plasminogen activator (tPA) is known to promote neuronal remodeling in the CNS, no mechanism of how this plastic function takes place has been reported so far. We provide here in vitro and in vivo demonstrations that this serine protease neutralizes inhibitory chondroitin sulfate proteoglycans (CSPGs) by promoting their degradation via the direct activation of endogenous type 4 disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4). Accordingly, in a model of compression-induced spinal cord injury (SCI) in rats, we found that administration of either tPA or its downstream effector ADAMTS-4 restores the tPA-dependent activity lost after the SCI and thereby, reduces content of CSPGs in the spinal cord, a cascade of events leading to an improved axonal regeneration/sprouting and eventually long term functional recovery. This is the first study to reveal a tPA-ADAMTS-4 axis and its function in the CNS. It also raises the prospect of exploiting such cooperation as a therapeutic tool for enhancing recovery after acute CNS injuries.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 66, June 2014, Pages 28-42
Journal: Neurobiology of Disease - Volume 66, June 2014, Pages 28-42
نویسندگان
Sighild Lemarchant, Mathilde Pruvost, Marie Hébert, Maxime Gauberti, Yannick Hommet, Aurélien Briens, Eric Maubert, Yatma Gueye, François Féron, Didier Petite, Marcel Mersel, Jean-Claude do Rego, Hubert Vaudry, Jari Koistinaho, Carine Ali,